TY  - CONF
AU  - Novaković, Andrea
AU  - Radovanović, Ljiljana
AU  - Petrović, Jelena
AU  - Šaponjić, Jasna
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5841
AB  - We examined the effects of ketamine/diazepam and propofol anesthesia on
hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV)-expressing
interneurons in the rat.
A total of 20 adult male Wistar rats were divided into two experimental groups - half
were anesthetized with ketamine/diazepam (100 mg/kg, Zoletil® 50), and the other
half received propofol anesthesia (100 mg/kg; Propofol Lipuro 2% (20mg/ml). We
performed immunohistochemistry protocols for PV and postsynaptic density protein
95 (PSD-95) staining on free-floating 40-µm brain slices. We used PSD-95 as an
excitatory synaptic marker to test local excitation changes along with changes in PV
expression.
Our results show significant suppression of GABAergic PV-expressing interneurons
during ketamine/diazepam anesthesia compared with propofol anesthesia, in the
dentate gyrus and CA3 regions of the hippocampus (z ≥ -4.16, p ≤ 10-3), and in the
RT. Moreover, this suppression resulted in an increase in PSD-95 expression only in
the hippocampus of rats anesthetized with ketamine/diazepam. Topographically
distinct effects of propofol anesthesia were not detected.
The observed imbalance between excitation and inhibition at the level of the
hippocampus during ketamine/diazepam anesthesia could be a consequence of lower
interneuronal GABA activity. Conversely, the topographically uniform expression of
PSD-95 during propofol anesthesia together with higher expression of GABAergic
interneurons could possibly indicate a stronger effect of GABA-mediated inhibition in
the hippocampus compared with ketamine/diazepam anesthesia.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Effects of different anesthetics on hippocampal and reticulothalamic GABAergic parvalbumin-expressing interneurons
IS  - 52
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5841
ER  - 

@conference{
author = "Novaković, Andrea and Radovanović, Ljiljana and Petrović, Jelena and Šaponjić, Jasna",
year = "2023",
abstract = "We examined the effects of ketamine/diazepam and propofol anesthesia on
hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV)-expressing
interneurons in the rat.
A total of 20 adult male Wistar rats were divided into two experimental groups - half
were anesthetized with ketamine/diazepam (100 mg/kg, Zoletil® 50), and the other
half received propofol anesthesia (100 mg/kg; Propofol Lipuro 2% (20mg/ml). We
performed immunohistochemistry protocols for PV and postsynaptic density protein
95 (PSD-95) staining on free-floating 40-µm brain slices. We used PSD-95 as an
excitatory synaptic marker to test local excitation changes along with changes in PV
expression.
Our results show significant suppression of GABAergic PV-expressing interneurons
during ketamine/diazepam anesthesia compared with propofol anesthesia, in the
dentate gyrus and CA3 regions of the hippocampus (z ≥ -4.16, p ≤ 10-3), and in the
RT. Moreover, this suppression resulted in an increase in PSD-95 expression only in
the hippocampus of rats anesthetized with ketamine/diazepam. Topographically
distinct effects of propofol anesthesia were not detected.
The observed imbalance between excitation and inhibition at the level of the
hippocampus during ketamine/diazepam anesthesia could be a consequence of lower
interneuronal GABA activity. Conversely, the topographically uniform expression of
PSD-95 during propofol anesthesia together with higher expression of GABAergic
interneurons could possibly indicate a stronger effect of GABA-mediated inhibition in
the hippocampus compared with ketamine/diazepam anesthesia.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Effects of different anesthetics on hippocampal and reticulothalamic GABAergic parvalbumin-expressing interneurons",
number = "52",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5841"
}

Novaković, A., Radovanović, L., Petrović, J.,& Šaponjić, J.. (2023). Effects of different anesthetics on hippocampal and reticulothalamic GABAergic parvalbumin-expressing interneurons. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society.(52).
https://hdl.handle.net/21.15107/rcub_ibiss_5841

Novaković A, Radovanović L, Petrović J, Šaponjić J. Effects of different anesthetics on hippocampal and reticulothalamic GABAergic parvalbumin-expressing interneurons. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;(52).
https://hdl.handle.net/21.15107/rcub_ibiss_5841 .

Novaković, Andrea, Radovanović, Ljiljana, Petrović, Jelena, Šaponjić, Jasna, "Effects of different anesthetics on hippocampal and reticulothalamic GABAergic parvalbumin-expressing interneurons" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia, no. 52 (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_5841 .

TY  - CONF
AU  - Šaponjić, Jasna
AU  - Radovanović, Ljiljana
AU  - Novaković, Andrea
AU  - Petrović, Jelena
PY  - 2023
UR  - https://esleepeurope.eu/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6243
AB  - Background: The GABAergic mechanism is an important target for the action of anesthetics and the promotion of sleep. We investigated the changes in
hippocampal and reticulo-thalamic nucleus (RT) GABAergic parvalbumin (PV)-expressing interneurons as possible underlying mechanisms of the different
local cortical and hippocampal EEG microstructures during NREM sleep compared with anesthesia-induced unconsciousness by two anesthetics with
different main mechanisms of action.
Methods: Twenty adult male Wistar rats were implanted for sleep recordings. After 3 hours of sleep recording, half of the rats were anesthetized with
ketamine/diazepam (100 mg/kg, i.p.) and the other half with propofol (100 mg/kg, i.p.). We recorded EEGs of the motor cortex and hippocampus during the
one-hour stable surgical phase of both anesthetics. The EEG microstructures of the motor cortex and hippocampus in local NREM sleep were compared with
their EEG microstructures during 30 minutes of unconsciousness induced by a given anesthetic. At the end of each recording under stable anesthesia, rats
were sacrificed for further PV and postsynaptic density protein 95 (PSD-95) immunohistochemistry.
Results: All three states of unconsciousness differed in motor cortical and hippocampal EEG microstructures (χ2≥9.46;p≤0.01). During propofol-induced
unconsciousness, attenuated delta and augmented sigma/beta amplitudes (z≥-4.13;p≤0.01) were the globally expressed difference, whereas increased
gamma amplitude (z=2.35;p=0.02) was the only difference at the motor-cortical level compared to NREM sleep. During ketamine/diazepam-induced
unconsciousness, attenuated theta (z≥-5.53;p≤10-4) and increased beta/gamma amplitudes (z≥-4.82;p≤10-4) were the globally expressed difference from
NREM sleep. Both anesthesia-induced unconsciousness expressed globally as increased beta amplitude (z≥-4.13;p≤10-3) and increased motor-cortical
gamma amplitude (z≥-4.20;p≤0.02) compared to NREM sleep. In contrast to propofol anesthesia, there was significant suppression of PV expression in the
hippocampus (z≤-2.71;p≤ .01) and RT during ketamine/diazepam anesthesia in all rats, but only in the hippocampus was there an inhibitory/excitatory
imbalance (increased PSD-95 expression).
Conclusions: Although anesthesia and sleep share many neurobiological features, they are distinct states in terms of local EEG microstructure and
underlying GABAergic and molecular substrate in local neuronal networks.
PB  - European Sleep Research Society
C3  - eSLEEP EUROPE; 2023 Oct 4-6; Online
T1  - GABAergic parvalbumin-expressing interneurons underlie distinct local EEG microstructure during different states of unconsciousness in rats
SP  - 2
EP  - 2
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6243
ER  - 

@conference{
author = "Šaponjić, Jasna and Radovanović, Ljiljana and Novaković, Andrea and Petrović, Jelena",
year = "2023",
abstract = "Background: The GABAergic mechanism is an important target for the action of anesthetics and the promotion of sleep. We investigated the changes in
hippocampal and reticulo-thalamic nucleus (RT) GABAergic parvalbumin (PV)-expressing interneurons as possible underlying mechanisms of the different
local cortical and hippocampal EEG microstructures during NREM sleep compared with anesthesia-induced unconsciousness by two anesthetics with
different main mechanisms of action.
Methods: Twenty adult male Wistar rats were implanted for sleep recordings. After 3 hours of sleep recording, half of the rats were anesthetized with
ketamine/diazepam (100 mg/kg, i.p.) and the other half with propofol (100 mg/kg, i.p.). We recorded EEGs of the motor cortex and hippocampus during the
one-hour stable surgical phase of both anesthetics. The EEG microstructures of the motor cortex and hippocampus in local NREM sleep were compared with
their EEG microstructures during 30 minutes of unconsciousness induced by a given anesthetic. At the end of each recording under stable anesthesia, rats
were sacrificed for further PV and postsynaptic density protein 95 (PSD-95) immunohistochemistry.
Results: All three states of unconsciousness differed in motor cortical and hippocampal EEG microstructures (χ2≥9.46;p≤0.01). During propofol-induced
unconsciousness, attenuated delta and augmented sigma/beta amplitudes (z≥-4.13;p≤0.01) were the globally expressed difference, whereas increased
gamma amplitude (z=2.35;p=0.02) was the only difference at the motor-cortical level compared to NREM sleep. During ketamine/diazepam-induced
unconsciousness, attenuated theta (z≥-5.53;p≤10-4) and increased beta/gamma amplitudes (z≥-4.82;p≤10-4) were the globally expressed difference from
NREM sleep. Both anesthesia-induced unconsciousness expressed globally as increased beta amplitude (z≥-4.13;p≤10-3) and increased motor-cortical
gamma amplitude (z≥-4.20;p≤0.02) compared to NREM sleep. In contrast to propofol anesthesia, there was significant suppression of PV expression in the
hippocampus (z≤-2.71;p≤ .01) and RT during ketamine/diazepam anesthesia in all rats, but only in the hippocampus was there an inhibitory/excitatory
imbalance (increased PSD-95 expression).
Conclusions: Although anesthesia and sleep share many neurobiological features, they are distinct states in terms of local EEG microstructure and
underlying GABAergic and molecular substrate in local neuronal networks.",
publisher = "European Sleep Research Society",
journal = "eSLEEP EUROPE; 2023 Oct 4-6; Online",
title = "GABAergic parvalbumin-expressing interneurons underlie distinct local EEG microstructure during different states of unconsciousness in rats",
pages = "2-2",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6243"
}

Šaponjić, J., Radovanović, L., Novaković, A.,& Petrović, J.. (2023). GABAergic parvalbumin-expressing interneurons underlie distinct local EEG microstructure during different states of unconsciousness in rats. in eSLEEP EUROPE; 2023 Oct 4-6; Online
European Sleep Research Society., 2-2.
https://hdl.handle.net/21.15107/rcub_ibiss_6243

Šaponjić J, Radovanović L, Novaković A, Petrović J. GABAergic parvalbumin-expressing interneurons underlie distinct local EEG microstructure during different states of unconsciousness in rats. in eSLEEP EUROPE; 2023 Oct 4-6; Online. 2023;:2-2.
https://hdl.handle.net/21.15107/rcub_ibiss_6243 .

Šaponjić, Jasna, Radovanović, Ljiljana, Novaković, Andrea, Petrović, Jelena, "GABAergic parvalbumin-expressing interneurons underlie distinct local EEG microstructure during different states of unconsciousness in rats" in eSLEEP EUROPE; 2023 Oct 4-6; Online (2023):2-2,
https://hdl.handle.net/21.15107/rcub_ibiss_6243 .

TY  - CONF
AU  - Radovanović, Ljiljana
AU  - Šaponjić, Jasna
AU  - Petrović, Jelena
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5828
AB  - We investigated the role of hippocampal GABAergic parvalbumin-expressing (PV)
interneurons in spatial and hippocampus-dependent memory abilities in rat models of
Parkinson's disease (PD).
Experiments were performed in adult male Wistar rats, including physiological
controls (n=14) and toxin lesion-induced PD models: PD cholinopathy (n=10),
hemiparkinsonism (n=7), and hemiparkinsonism with PD cholinopathy (n=6).
Behavioral assessments and PV immunohistochemistry were performed 14 and 42
days after lesions. Spatial habituation test and novel object recognition test were used
to assess spatial and hippocampus-dependent short- and long-term recognition
memory.
All experimental groups had no motor impairments during the follow-up period
(X2
≥2.01, p≥0.07). Although hippocampal PV expression remained unchanged over
time in PD cholinopathy (z≥-1.91, p≥0.06), we evidenced impairments in spatial,
short- and long-term recognition memory, but only at day 42 (X2
≥0.38, p=0.83;
t=0.13, p=0.91). In the hemiparkinsonian rats, unchanged hippocampal PV expression
(z≥-1.52, p≥0.14) was followed by impairment in spatial memory (X2
≥2.87, p≥0.22),
but both recognition memories were intact over time (t≥3.16, p≤0.03). In the
hemiparkinsonian rats with PD cholinopathy, long-lasting impairment of spatial
memory (X2
≥0.72, p≥0.22) was followed by delayed short- and long-term impairment
of recognition memory (t=-0.24, p=0.82) along with hippocampal PV suppression
(z=-3.17, p=10-3), which was functionally coupled to impairment of recognition
memory (r=0.52, p=0.04).
Our results suggest that dopaminergic denervation plays an important role in
impairing spatial memory in the prodromal stage of PD, whereas cholinergic
denervation and hippocampal PV suppression impair short- and long-term memory in
a delayed manner in PD cholinopathy and hemiparkinsonism with PD cholinopathy.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - GABAergic parvalbumin-expressing interneurons play a role in memory impairment in rat models of Parkinson's disease
IS  - 49
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5828
ER  - 

@conference{
author = "Radovanović, Ljiljana and Šaponjić, Jasna and Petrović, Jelena",
year = "2023",
abstract = "We investigated the role of hippocampal GABAergic parvalbumin-expressing (PV)
interneurons in spatial and hippocampus-dependent memory abilities in rat models of
Parkinson's disease (PD).
Experiments were performed in adult male Wistar rats, including physiological
controls (n=14) and toxin lesion-induced PD models: PD cholinopathy (n=10),
hemiparkinsonism (n=7), and hemiparkinsonism with PD cholinopathy (n=6).
Behavioral assessments and PV immunohistochemistry were performed 14 and 42
days after lesions. Spatial habituation test and novel object recognition test were used
to assess spatial and hippocampus-dependent short- and long-term recognition
memory.
All experimental groups had no motor impairments during the follow-up period
(X2
≥2.01, p≥0.07). Although hippocampal PV expression remained unchanged over
time in PD cholinopathy (z≥-1.91, p≥0.06), we evidenced impairments in spatial,
short- and long-term recognition memory, but only at day 42 (X2
≥0.38, p=0.83;
t=0.13, p=0.91). In the hemiparkinsonian rats, unchanged hippocampal PV expression
(z≥-1.52, p≥0.14) was followed by impairment in spatial memory (X2
≥2.87, p≥0.22),
but both recognition memories were intact over time (t≥3.16, p≤0.03). In the
hemiparkinsonian rats with PD cholinopathy, long-lasting impairment of spatial
memory (X2
≥0.72, p≥0.22) was followed by delayed short- and long-term impairment
of recognition memory (t=-0.24, p=0.82) along with hippocampal PV suppression
(z=-3.17, p=10-3), which was functionally coupled to impairment of recognition
memory (r=0.52, p=0.04).
Our results suggest that dopaminergic denervation plays an important role in
impairing spatial memory in the prodromal stage of PD, whereas cholinergic
denervation and hippocampal PV suppression impair short- and long-term memory in
a delayed manner in PD cholinopathy and hemiparkinsonism with PD cholinopathy.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "GABAergic parvalbumin-expressing interneurons play a role in memory impairment in rat models of Parkinson's disease",
number = "49",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5828"
}

Radovanović, L., Šaponjić, J.,& Petrović, J.. (2023). GABAergic parvalbumin-expressing interneurons play a role in memory impairment in rat models of Parkinson's disease. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society.(49).
https://hdl.handle.net/21.15107/rcub_ibiss_5828

Radovanović L, Šaponjić J, Petrović J. GABAergic parvalbumin-expressing interneurons play a role in memory impairment in rat models of Parkinson's disease. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;(49).
https://hdl.handle.net/21.15107/rcub_ibiss_5828 .

Radovanović, Ljiljana, Šaponjić, Jasna, Petrović, Jelena, "GABAergic parvalbumin-expressing interneurons play a role in memory impairment in rat models of Parkinson's disease" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia, no. 49 (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_5828 .

TY  - CONF
AU  - Novaković, Andrea
AU  - Radovanović, Ljiljana
AU  - Petrović, Jelena
AU  - Šaponjić, Jasna
PY  - 2023
UR  - https://fensrm2023algarve.pt/scientific-programme/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5810
AB  - We examined the effects of ketamine/diazepam and propofol anesthesia on hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV)-expressing interneurons in the rat.
A total of 20 adult male Wistar rats were divided into two experimental groups - half were anesthetized with ketamine/diazepam (100 mg/kg, Zoletil® 50), and the other half received propofol anesthesia (100 mg/kg; Propofol Lipuro 2% (20mg/ml). We performed immunohistochemistry protocols for PV and postsynaptic density protein 95 (PSD-95) staining on free-floating 40-µm brain slices. We used PSD-95 as an excitatory synaptic marker to test local excitation changes along with changes in PV expression.
Our results show significant suppression of GABAergic PV-expressing interneurons during ketamine/diazepam anesthesia compared with propofol anesthesia, in the dentate gyrus and CA3 regions of the hippocampus, and in the RT. Moreover, this suppression resulted in an increase in PSD-95 expression only in the hippocampus of rats anesthetized with ketamine/diazepam. Topographically distinct effects of propofol anesthesia were not detected.
The observed imbalance between excitation and inhibition at the level of the hippocampus during ketamine/diazepam anesthesia could be a consequence of lower interneuronal GABA activity. Conversely, the topographically uniform expression of PSD-95 during propofol anesthesia together with higher expression of GABAergic interneurons could possibly indicate a stronger effect of GABA-mediated inhibition in the hippocampus compared with ketamine/diazepam anesthesia.
PB  - Federation of European Neuroscience Societies
C3  - FENS Regional Meeting: FRM 2023; 2023 May 3-5; Algarve, Portugal
T1  - Topographical effects of different anesthetics on GABAergic parvalbumin interneurons in rat
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5810
ER  - 

@conference{
author = "Novaković, Andrea and Radovanović, Ljiljana and Petrović, Jelena and Šaponjić, Jasna",
year = "2023",
abstract = "We examined the effects of ketamine/diazepam and propofol anesthesia on hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV)-expressing interneurons in the rat.
A total of 20 adult male Wistar rats were divided into two experimental groups - half were anesthetized with ketamine/diazepam (100 mg/kg, Zoletil® 50), and the other half received propofol anesthesia (100 mg/kg; Propofol Lipuro 2% (20mg/ml). We performed immunohistochemistry protocols for PV and postsynaptic density protein 95 (PSD-95) staining on free-floating 40-µm brain slices. We used PSD-95 as an excitatory synaptic marker to test local excitation changes along with changes in PV expression.
Our results show significant suppression of GABAergic PV-expressing interneurons during ketamine/diazepam anesthesia compared with propofol anesthesia, in the dentate gyrus and CA3 regions of the hippocampus, and in the RT. Moreover, this suppression resulted in an increase in PSD-95 expression only in the hippocampus of rats anesthetized with ketamine/diazepam. Topographically distinct effects of propofol anesthesia were not detected.
The observed imbalance between excitation and inhibition at the level of the hippocampus during ketamine/diazepam anesthesia could be a consequence of lower interneuronal GABA activity. Conversely, the topographically uniform expression of PSD-95 during propofol anesthesia together with higher expression of GABAergic interneurons could possibly indicate a stronger effect of GABA-mediated inhibition in the hippocampus compared with ketamine/diazepam anesthesia.",
publisher = "Federation of European Neuroscience Societies",
journal = "FENS Regional Meeting: FRM 2023; 2023 May 3-5; Algarve, Portugal",
title = "Topographical effects of different anesthetics on GABAergic parvalbumin interneurons in rat",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5810"
}

Novaković, A., Radovanović, L., Petrović, J.,& Šaponjić, J.. (2023). Topographical effects of different anesthetics on GABAergic parvalbumin interneurons in rat. in FENS Regional Meeting: FRM 2023; 2023 May 3-5; Algarve, Portugal
Federation of European Neuroscience Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5810

Novaković A, Radovanović L, Petrović J, Šaponjić J. Topographical effects of different anesthetics on GABAergic parvalbumin interneurons in rat. in FENS Regional Meeting: FRM 2023; 2023 May 3-5; Algarve, Portugal. 2023;.
https://hdl.handle.net/21.15107/rcub_ibiss_5810 .

Novaković, Andrea, Radovanović, Ljiljana, Petrović, Jelena, Šaponjić, Jasna, "Topographical effects of different anesthetics on GABAergic parvalbumin interneurons in rat" in FENS Regional Meeting: FRM 2023; 2023 May 3-5; Algarve, Portugal (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_5810 .

TY  - JOUR
AU  - Radovanović, Ljiljana
AU  - Novaković, Andrea
AU  - Petrović, Jelena
AU  - Šaponjić, Jasna
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5547
AB  - We traced the changes in GABAergic parvalbumin (PV)-expressing interneurons of the hippocampus and reticulo-thalamic nucleus (RT) as possible underlying mechanisms of the different local cortical and hippocampal electroencephalographic (EEG) microstructures during the non-rapid-eye movement (NREM) sleep compared with anesthesia-induced unconsciousness by two anesthetics with different main mechanisms of action (ketamine/diazepam versus propofol). After 3 h of recording their sleep, the rats were divided into two experimental groups: one half received ketamine/diazepam anesthesia and the other half received propofol anesthesia. We simultaneously recorded the EEG of the motor cortex and hippocampus during sleep and during 1 h of surgical anesthesia. We performed immunohistochemistry and analyzed the PV and postsynaptic density protein 95 (PSD-95) expression. PV suppression in the hippocampus and at RT underlies the global theta amplitude attenuation and hippocampal gamma augmentation that is a unique feature of ketamine-induced versus propofol-induced unconsciousness and NREM sleep. While PV suppression resulted in an increase in hippocampal PSD-95 expression, there was no imbalance between inhibition and excitation during ketamine/diazepam anesthesia compared with propofol anesthesia in RT. This increased excitation could be a consequence of a lower GABA interneuronal activity and an additional mechanism underlying the unique local EEG microstructure in the hippocampus during ketamine/diazepam anesthesia.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness
IS  - 7
VL  - 24
DO  - 10.3390/ijms24076769
SP  - 6769
ER  - 

@article{
author = "Radovanović, Ljiljana and Novaković, Andrea and Petrović, Jelena and Šaponjić, Jasna",
year = "2023",
abstract = "We traced the changes in GABAergic parvalbumin (PV)-expressing interneurons of the hippocampus and reticulo-thalamic nucleus (RT) as possible underlying mechanisms of the different local cortical and hippocampal electroencephalographic (EEG) microstructures during the non-rapid-eye movement (NREM) sleep compared with anesthesia-induced unconsciousness by two anesthetics with different main mechanisms of action (ketamine/diazepam versus propofol). After 3 h of recording their sleep, the rats were divided into two experimental groups: one half received ketamine/diazepam anesthesia and the other half received propofol anesthesia. We simultaneously recorded the EEG of the motor cortex and hippocampus during sleep and during 1 h of surgical anesthesia. We performed immunohistochemistry and analyzed the PV and postsynaptic density protein 95 (PSD-95) expression. PV suppression in the hippocampus and at RT underlies the global theta amplitude attenuation and hippocampal gamma augmentation that is a unique feature of ketamine-induced versus propofol-induced unconsciousness and NREM sleep. While PV suppression resulted in an increase in hippocampal PSD-95 expression, there was no imbalance between inhibition and excitation during ketamine/diazepam anesthesia compared with propofol anesthesia in RT. This increased excitation could be a consequence of a lower GABA interneuronal activity and an additional mechanism underlying the unique local EEG microstructure in the hippocampus during ketamine/diazepam anesthesia.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness",
number = "7",
volume = "24",
doi = "10.3390/ijms24076769",
pages = "6769"
}

Radovanović, L., Novaković, A., Petrović, J.,& Šaponjić, J.. (2023). Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness. in International Journal of Molecular Sciences
Basel: MDPI., 24(7), 6769.
https://doi.org/10.3390/ijms24076769

Radovanović L, Novaković A, Petrović J, Šaponjić J. Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness. in International Journal of Molecular Sciences. 2023;24(7):6769.
doi:10.3390/ijms24076769 .

Radovanović, Ljiljana, Novaković, Andrea, Petrović, Jelena, Šaponjić, Jasna, "Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness" in International Journal of Molecular Sciences, 24, no. 7 (2023):6769,
https://doi.org/10.3390/ijms24076769 . .

TY  - CONF
AU  - Radovanović, Ljiljana
AU  - Šaponjić, Jasna
AU  - Petrović, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5556
AB  - We investigated the alterations of reticulo-thalamic (RT) GABAergic parvalbumin (PV+) interneurons and synaptic reorganization underlying the altered hippocampal high voltage sleep spindle (HVS) dynamics during REM sleep in the rat
models of Parkinson’s disease (PD). Adult male Wistar rats were implanted for 6h sleep recording during light phase in four
experimental groups: control (implanted controls), PD cholinopathy (bilateral lesion of the nucleus pedunculopontinus
tegmentalis−PPT), hemiparkinsonism (unilateral lesion of the nucleus substantiae nigrae pars compacta−SNpc) and
hemiparkinsonism with PD cholinopathy (unilateral SNpc/bilateral PPT lesion). Following 14 days of the surgical procedure
we differentiated the Wake/NREM/REM 10s epochs, and the HVSs detection and extraction was done automatically (4.1–10
Hz band pass filter, 1s minimum duration) and visually validated. Hippocampal HVS dynamics were analyzed during 1h of
NREM/REM sleep. Alterations of the PV+ interneurons and synaptic re-organization within the RT were determined by the
parvalbumin, MAP2 and PSD-95 immunostaining. REM sleep is a predisposing state for the HVSs induction in all
experimental models of PD neuropathology. Whereas the PD cholinopathy induced the prolongation and higher density of
hippocampal HVSs, the hemiparkinsonism with PD cholinopathy increased the hippocampal HVSs intrinsic frequency during
REM sleep. In contrast to the unaltered PV+ interneurons/partially enhanced MAP2/suppressed PSD-95 expression during
PD cholinopathy, we evidenced the PV+ interneurons reduction/enhanced MAP2/no change of PSD-95 expression in the RT
during hemiparkinsonism with PD cholinopathy. Distinct PV+ interneurons alteration and inhibition/excitation balance in the
RT could be the underlying mechanisms of HVS generation/alteration during REM sleep in the parkinsonian rats.
PB  - Federation of European Neuroscience Societies
C3  - E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France
T1  - Hippocampal sleep spindle dynamics during REM sleep and their distinct underlying parvalbumin and synaptic proteins expression in the reticulo-thalamic nucleus of the parkinsonian rats
SP  - 2231
EP  - 2232
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5556
ER  - 

@conference{
author = "Radovanović, Ljiljana and Šaponjić, Jasna and Petrović, Jelena",
year = "2022",
abstract = "We investigated the alterations of reticulo-thalamic (RT) GABAergic parvalbumin (PV+) interneurons and synaptic reorganization underlying the altered hippocampal high voltage sleep spindle (HVS) dynamics during REM sleep in the rat
models of Parkinson’s disease (PD). Adult male Wistar rats were implanted for 6h sleep recording during light phase in four
experimental groups: control (implanted controls), PD cholinopathy (bilateral lesion of the nucleus pedunculopontinus
tegmentalis−PPT), hemiparkinsonism (unilateral lesion of the nucleus substantiae nigrae pars compacta−SNpc) and
hemiparkinsonism with PD cholinopathy (unilateral SNpc/bilateral PPT lesion). Following 14 days of the surgical procedure
we differentiated the Wake/NREM/REM 10s epochs, and the HVSs detection and extraction was done automatically (4.1–10
Hz band pass filter, 1s minimum duration) and visually validated. Hippocampal HVS dynamics were analyzed during 1h of
NREM/REM sleep. Alterations of the PV+ interneurons and synaptic re-organization within the RT were determined by the
parvalbumin, MAP2 and PSD-95 immunostaining. REM sleep is a predisposing state for the HVSs induction in all
experimental models of PD neuropathology. Whereas the PD cholinopathy induced the prolongation and higher density of
hippocampal HVSs, the hemiparkinsonism with PD cholinopathy increased the hippocampal HVSs intrinsic frequency during
REM sleep. In contrast to the unaltered PV+ interneurons/partially enhanced MAP2/suppressed PSD-95 expression during
PD cholinopathy, we evidenced the PV+ interneurons reduction/enhanced MAP2/no change of PSD-95 expression in the RT
during hemiparkinsonism with PD cholinopathy. Distinct PV+ interneurons alteration and inhibition/excitation balance in the
RT could be the underlying mechanisms of HVS generation/alteration during REM sleep in the parkinsonian rats.",
publisher = "Federation of European Neuroscience Societies",
journal = "E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France",
title = "Hippocampal sleep spindle dynamics during REM sleep and their distinct underlying parvalbumin and synaptic proteins expression in the reticulo-thalamic nucleus of the parkinsonian rats",
pages = "2231-2232",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5556"
}

Radovanović, L., Šaponjić, J.,& Petrović, J.. (2022). Hippocampal sleep spindle dynamics during REM sleep and their distinct underlying parvalbumin and synaptic proteins expression in the reticulo-thalamic nucleus of the parkinsonian rats. in E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France
Federation of European Neuroscience Societies., 2231-2232.
https://hdl.handle.net/21.15107/rcub_ibiss_5556

Radovanović L, Šaponjić J, Petrović J. Hippocampal sleep spindle dynamics during REM sleep and their distinct underlying parvalbumin and synaptic proteins expression in the reticulo-thalamic nucleus of the parkinsonian rats. in E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France. 2022;:2231-2232.
https://hdl.handle.net/21.15107/rcub_ibiss_5556 .

Radovanović, Ljiljana, Šaponjić, Jasna, Petrović, Jelena, "Hippocampal sleep spindle dynamics during REM sleep and their distinct underlying parvalbumin and synaptic proteins expression in the reticulo-thalamic nucleus of the parkinsonian rats" in E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France (2022):2231-2232,
https://hdl.handle.net/21.15107/rcub_ibiss_5556 .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Radovanović, Ljiljana
AU  - Šaponjić, Jasna
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0166432820306562
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33038348
UR  - https://radar.ibiss.bg.ac.rs/123456789/3908
AB  - We investigated the prodromal alterations of local sleep, particularly the motor cortical and hippocampal sleep, along with spontaneous locomotor activity in the rat models of Parkinson's disease (PD). We performed our experiments in adult, male Wistar rats, chronically implanted for sleep recording and divided into four experimental groups: the control (implanted controls), the bilateral pedunculopontine tegmental nucleus (PPT) lesions (PD cholinopathy), the unilateral substantia nigra pars compacta (SNpc) lesions (hemiparkinsonism) and the unilateral SNpc/bilateral PPT lesions (hemiparkinsonism with PD cholinopathy). We followed their sleep, basal locomotor activity and spatial habituation for 14 days following the surgical procedures. Severe prodromal local sleep disturbances in the hemiparkinsonian rats were expressed as sleep fragmentation and distinct local NREM/REM EEG microstructure alterations in both the motor cortex and the hippocampus. Alongside the state-unrelated role of the dopaminergic control of theta oscillations and NREM/REM related sigma and beta oscillations, we demonstrated that the REM neurochemical regulatory substrate is particularly important in the dopaminergic control of beta oscillations. In addition, hippocampal prodromal sleep disorders in the hemiparkinsonian rats were expressed as NREM/REM fragmentation and the opposite impact of dopaminergic versus cholinergic control of the NREM delta and beta oscillation amplitudes in the hippocampus, likewise in the motor cortex versus the hippocampus. All these distinct prodromal local sleep disorders and the dopaminergic vs. cholinergic impact on NREM/REM EEG microstructure alterations are of fundamental importance for the further development and follow-up of PD-modifying therapies, and for the identification of patients who are at risk of developing PD.
PB  - Elsevier
T2  - Behavioural Brain Research
T1  - Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.
VL  - 397
DO  - 10.1016/j.bbr.2020.112957
SP  - 112957
ER  - 

@article{
author = "Petrović, Jelena and Radovanović, Ljiljana and Šaponjić, Jasna",
year = "2021",
abstract = "We investigated the prodromal alterations of local sleep, particularly the motor cortical and hippocampal sleep, along with spontaneous locomotor activity in the rat models of Parkinson's disease (PD). We performed our experiments in adult, male Wistar rats, chronically implanted for sleep recording and divided into four experimental groups: the control (implanted controls), the bilateral pedunculopontine tegmental nucleus (PPT) lesions (PD cholinopathy), the unilateral substantia nigra pars compacta (SNpc) lesions (hemiparkinsonism) and the unilateral SNpc/bilateral PPT lesions (hemiparkinsonism with PD cholinopathy). We followed their sleep, basal locomotor activity and spatial habituation for 14 days following the surgical procedures. Severe prodromal local sleep disturbances in the hemiparkinsonian rats were expressed as sleep fragmentation and distinct local NREM/REM EEG microstructure alterations in both the motor cortex and the hippocampus. Alongside the state-unrelated role of the dopaminergic control of theta oscillations and NREM/REM related sigma and beta oscillations, we demonstrated that the REM neurochemical regulatory substrate is particularly important in the dopaminergic control of beta oscillations. In addition, hippocampal prodromal sleep disorders in the hemiparkinsonian rats were expressed as NREM/REM fragmentation and the opposite impact of dopaminergic versus cholinergic control of the NREM delta and beta oscillation amplitudes in the hippocampus, likewise in the motor cortex versus the hippocampus. All these distinct prodromal local sleep disorders and the dopaminergic vs. cholinergic impact on NREM/REM EEG microstructure alterations are of fundamental importance for the further development and follow-up of PD-modifying therapies, and for the identification of patients who are at risk of developing PD.",
publisher = "Elsevier",
journal = "Behavioural Brain Research",
title = "Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.",
volume = "397",
doi = "10.1016/j.bbr.2020.112957",
pages = "112957"
}

Petrović, J., Radovanović, L.,& Šaponjić, J.. (2021). Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.. in Behavioural Brain Research
Elsevier., 397, 112957.
https://doi.org/10.1016/j.bbr.2020.112957

Petrović J, Radovanović L, Šaponjić J. Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.. in Behavioural Brain Research. 2021;397:112957.
doi:10.1016/j.bbr.2020.112957 .

Petrović, Jelena, Radovanović, Ljiljana, Šaponjić, Jasna, "Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy." in Behavioural Brain Research, 397 (2021):112957,
https://doi.org/10.1016/j.bbr.2020.112957 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Radovanović, Ljiljana
AU  - Šaponjić, Jasna
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0166432820306562
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33038348
UR  - https://radar.ibiss.bg.ac.rs/123456789/3908
UR  - https://radar.ibiss.bg.ac.rs/123456789/3909
AB  - We investigated the prodromal alterations of local sleep, particularly the motor cortical and hippocampal sleep, along with spontaneous locomotor activity in the rat models of Parkinson's disease (PD). We performed our experiments in adult, male Wistar rats, chronically implanted for sleep recording and divided into four experimental groups: the control (implanted controls), the bilateral pedunculopontine tegmental nucleus (PPT) lesions (PD cholinopathy), the unilateral substantia nigra pars compacta (SNpc) lesions (hemiparkinsonism) and the unilateral SNpc/bilateral PPT lesions (hemiparkinsonism with PD cholinopathy). We followed their sleep, basal locomotor activity and spatial habituation for 14 days following the surgical procedures. Severe prodromal local sleep disturbances in the hemiparkinsonian rats were expressed as sleep fragmentation and distinct local NREM/REM EEG microstructure alterations in both the motor cortex and the hippocampus. Alongside the state-unrelated role of the dopaminergic control of theta oscillations and NREM/REM related sigma and beta oscillations, we demonstrated that the REM neurochemical regulatory substrate is particularly important in the dopaminergic control of beta oscillations. In addition, hippocampal prodromal sleep disorders in the hemiparkinsonian rats were expressed as NREM/REM fragmentation and the opposite impact of dopaminergic versus cholinergic control of the NREM delta and beta oscillation amplitudes in the hippocampus, likewise in the motor cortex versus the hippocampus. All these distinct prodromal local sleep disorders and the dopaminergic vs. cholinergic impact on NREM/REM EEG microstructure alterations are of fundamental importance for the further development and follow-up of PD-modifying therapies, and for the identification of patients who are at risk of developing PD.
PB  - Elsevier
T2  - Behavioural Brain Research
T1  - Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.
VL  - 397
DO  - 10.1016/j.bbr.2020.112957
SP  - 112957
ER  - 

@article{
author = "Petrović, Jelena and Radovanović, Ljiljana and Šaponjić, Jasna",
year = "2021",
abstract = "We investigated the prodromal alterations of local sleep, particularly the motor cortical and hippocampal sleep, along with spontaneous locomotor activity in the rat models of Parkinson's disease (PD). We performed our experiments in adult, male Wistar rats, chronically implanted for sleep recording and divided into four experimental groups: the control (implanted controls), the bilateral pedunculopontine tegmental nucleus (PPT) lesions (PD cholinopathy), the unilateral substantia nigra pars compacta (SNpc) lesions (hemiparkinsonism) and the unilateral SNpc/bilateral PPT lesions (hemiparkinsonism with PD cholinopathy). We followed their sleep, basal locomotor activity and spatial habituation for 14 days following the surgical procedures. Severe prodromal local sleep disturbances in the hemiparkinsonian rats were expressed as sleep fragmentation and distinct local NREM/REM EEG microstructure alterations in both the motor cortex and the hippocampus. Alongside the state-unrelated role of the dopaminergic control of theta oscillations and NREM/REM related sigma and beta oscillations, we demonstrated that the REM neurochemical regulatory substrate is particularly important in the dopaminergic control of beta oscillations. In addition, hippocampal prodromal sleep disorders in the hemiparkinsonian rats were expressed as NREM/REM fragmentation and the opposite impact of dopaminergic versus cholinergic control of the NREM delta and beta oscillation amplitudes in the hippocampus, likewise in the motor cortex versus the hippocampus. All these distinct prodromal local sleep disorders and the dopaminergic vs. cholinergic impact on NREM/REM EEG microstructure alterations are of fundamental importance for the further development and follow-up of PD-modifying therapies, and for the identification of patients who are at risk of developing PD.",
publisher = "Elsevier",
journal = "Behavioural Brain Research",
title = "Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.",
volume = "397",
doi = "10.1016/j.bbr.2020.112957",
pages = "112957"
}

Petrović, J., Radovanović, L.,& Šaponjić, J.. (2021). Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.. in Behavioural Brain Research
Elsevier., 397, 112957.
https://doi.org/10.1016/j.bbr.2020.112957

Petrović J, Radovanović L, Šaponjić J. Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.. in Behavioural Brain Research. 2021;397:112957.
doi:10.1016/j.bbr.2020.112957 .

Petrović, Jelena, Radovanović, Ljiljana, Šaponjić, Jasna, "Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy." in Behavioural Brain Research, 397 (2021):112957,
https://doi.org/10.1016/j.bbr.2020.112957 . .

TY  - JOUR
AU  - Radovanović, Ljiljana
AU  - Petrović, Jelena
AU  - Šaponjić, Jasna
PY  - 2021
UR  - https://www.mdpi.com/1422-0067/22/16/8922
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4460
AB  - We investigated the alterations of hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV) interneurons and their synaptic re-organizations underlying the prodromal local sleep disorders in the distinct rat models of Parkinson’s disease (PD). We demonstrated for the first time that REM sleep is a predisposing state for the high-voltage sleep spindles (HVS) induction in all experimental models of PD, particularly during hippocampal REM sleep in the hemiparkinsonian models. There were the opposite underlying alterations of the hippocampal and RT GABAergic PV+ interneurons along with the distinct MAP2 and PSD-95 expressions. Whereas the PD cholinopathy enhanced the number of PV+ interneurons and suppressed the MAP2/PSD-95 expression, the hemiparkinsonism with PD cholinopathy reduced the number of PV+ interneurons and enhanced the MAP2/PSD-95 expression in the hippocampus. Whereas the PD cholinopathy did not alter PV+ interneurons but partially enhanced MAP2 and suppressed PSD-95 expression remotely in the RT, the hemiparkinsonism with PD cholinopathy reduced the PV+ interneurons, enhanced MAP2, and did not change PSD-95 expression remotely in the RT. Our study demonstrates for the first time an important regulatory role of the hippocampal and RT GABAergic PV+ interneurons and the synaptic protein dynamic alterations in the distinct rat models of PD neuropathology.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson’s Disease Neuropathology
IS  - 16
VL  - 22
DO  - 10.3390/ijms22168922
SP  - 8922
ER  - 

@article{
author = "Radovanović, Ljiljana and Petrović, Jelena and Šaponjić, Jasna",
year = "2021",
abstract = "We investigated the alterations of hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV) interneurons and their synaptic re-organizations underlying the prodromal local sleep disorders in the distinct rat models of Parkinson’s disease (PD). We demonstrated for the first time that REM sleep is a predisposing state for the high-voltage sleep spindles (HVS) induction in all experimental models of PD, particularly during hippocampal REM sleep in the hemiparkinsonian models. There were the opposite underlying alterations of the hippocampal and RT GABAergic PV+ interneurons along with the distinct MAP2 and PSD-95 expressions. Whereas the PD cholinopathy enhanced the number of PV+ interneurons and suppressed the MAP2/PSD-95 expression, the hemiparkinsonism with PD cholinopathy reduced the number of PV+ interneurons and enhanced the MAP2/PSD-95 expression in the hippocampus. Whereas the PD cholinopathy did not alter PV+ interneurons but partially enhanced MAP2 and suppressed PSD-95 expression remotely in the RT, the hemiparkinsonism with PD cholinopathy reduced the PV+ interneurons, enhanced MAP2, and did not change PSD-95 expression remotely in the RT. Our study demonstrates for the first time an important regulatory role of the hippocampal and RT GABAergic PV+ interneurons and the synaptic protein dynamic alterations in the distinct rat models of PD neuropathology.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson’s Disease Neuropathology",
number = "16",
volume = "22",
doi = "10.3390/ijms22168922",
pages = "8922"
}

Radovanović, L., Petrović, J.,& Šaponjić, J.. (2021). Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson’s Disease Neuropathology. in International Journal of Molecular Sciences
Basel: MDPI., 22(16), 8922.
https://doi.org/10.3390/ijms22168922

Radovanović L, Petrović J, Šaponjić J. Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson’s Disease Neuropathology. in International Journal of Molecular Sciences. 2021;22(16):8922.
doi:10.3390/ijms22168922 .

Radovanović, Ljiljana, Petrović, Jelena, Šaponjić, Jasna, "Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson’s Disease Neuropathology" in International Journal of Molecular Sciences, 22, no. 16 (2021):8922,
https://doi.org/10.3390/ijms22168922 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Radovanović, Ljiljana
AU  - Šaponjić, Jasna
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1111/jsr.13090
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32472657
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3696
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3707
AB  - We investigated the homogeneity/heterogeneity of spontaneous sleep, simultaneously recorded in the motor cortex and the hippocampus of control rats, and particularly analysed simultaneous and non-simultaneous motor cortical and hippocampal non-rapid eye movement (NREM)/rapid eye movement (REM) sleep. We demonstrate that the sleep architectures of the motor cortex and hippocampus are different in control rats. There was an increase of NREM duration and a decrease of REM duration in the hippocampus versus the motor cortex. In terms of duration, NREM state is the most heterogeneous in the hippocampus, whereas the REM state is the most heterogeneous in the motor cortex. Whereas the hippocampal NREM duration was increased due to the prolongation of NREM episodes, the hippocampal REM duration decreased due to the decreased number of REM episodes. The heterogeneity of sleep in the motor cortex and hippocampus in control rats was particularly expressed through the inverse alteration of sigma amplitude during NREM sleep and beta/gamma amplitudes during REM sleep in the hippocampus, along with the delta, sigma, beta and gamma amplitudes only during non-simultaneous NREM/REM sleep in the hippocampus. We demonstrated the brain structure-related and NREM/REM state-related heterogeneity of the motor cortical and hippocampal local sleep in control rats. The distinctly altered local NREM/REM states, alongside their episode dynamics and electroencephalographic (EEG) microstructures, suggest the importance of both the local neuronal network substrate and the NREM/REM neurochemical substrate in the control mechanisms of sleep.
PB  - Blackwell Publishing Ltd
T2  - Journal of Sleep Research
T1  - Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.
DO  - 10.1111/jsr.13090
SP  - e13090
ER  - 

@article{
author = "Petrović, Jelena and Radovanović, Ljiljana and Šaponjić, Jasna",
year = "2020",
abstract = "We investigated the homogeneity/heterogeneity of spontaneous sleep, simultaneously recorded in the motor cortex and the hippocampus of control rats, and particularly analysed simultaneous and non-simultaneous motor cortical and hippocampal non-rapid eye movement (NREM)/rapid eye movement (REM) sleep. We demonstrate that the sleep architectures of the motor cortex and hippocampus are different in control rats. There was an increase of NREM duration and a decrease of REM duration in the hippocampus versus the motor cortex. In terms of duration, NREM state is the most heterogeneous in the hippocampus, whereas the REM state is the most heterogeneous in the motor cortex. Whereas the hippocampal NREM duration was increased due to the prolongation of NREM episodes, the hippocampal REM duration decreased due to the decreased number of REM episodes. The heterogeneity of sleep in the motor cortex and hippocampus in control rats was particularly expressed through the inverse alteration of sigma amplitude during NREM sleep and beta/gamma amplitudes during REM sleep in the hippocampus, along with the delta, sigma, beta and gamma amplitudes only during non-simultaneous NREM/REM sleep in the hippocampus. We demonstrated the brain structure-related and NREM/REM state-related heterogeneity of the motor cortical and hippocampal local sleep in control rats. The distinctly altered local NREM/REM states, alongside their episode dynamics and electroencephalographic (EEG) microstructures, suggest the importance of both the local neuronal network substrate and the NREM/REM neurochemical substrate in the control mechanisms of sleep.",
publisher = "Blackwell Publishing Ltd",
journal = "Journal of Sleep Research",
title = "Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.",
doi = "10.1111/jsr.13090",
pages = "e13090"
}

Petrović, J., Radovanović, L.,& Šaponjić, J.. (2020). Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.. in Journal of Sleep Research
Blackwell Publishing Ltd., e13090.
https://doi.org/10.1111/jsr.13090

Petrović J, Radovanović L, Šaponjić J. Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.. in Journal of Sleep Research. 2020;:e13090.
doi:10.1111/jsr.13090 .

Petrović, Jelena, Radovanović, Ljiljana, Šaponjić, Jasna, "Diversity of simultaneous sleep in the motor cortex and hippocampus in rats." in Journal of Sleep Research (2020):e13090,
https://doi.org/10.1111/jsr.13090 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Radovanović, Ljiljana
AU  - Šaponjić, Jasna
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1111/jsr.13090
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32472657
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3696
UR  - https://radar.ibiss.bg.ac.rs/handle/handle/123456789/3707
AB  - We investigated the homogeneity/heterogeneity of spontaneous sleep, simultaneously recorded in the motor cortex and the hippocampus of control rats, and particularly analysed simultaneous and non-simultaneous motor cortical and hippocampal non-rapid eye movement (NREM)/rapid eye movement (REM) sleep. We demonstrate that the sleep architectures of the motor cortex and hippocampus are different in control rats. There was an increase of NREM duration and a decrease of REM duration in the hippocampus versus the motor cortex. In terms of duration, NREM state is the most heterogeneous in the hippocampus, whereas the REM state is the most heterogeneous in the motor cortex. Whereas the hippocampal NREM duration was increased due to the prolongation of NREM episodes, the hippocampal REM duration decreased due to the decreased number of REM episodes. The heterogeneity of sleep in the motor cortex and hippocampus in control rats was particularly expressed through the inverse alteration of sigma amplitude during NREM sleep and beta/gamma amplitudes during REM sleep in the hippocampus, along with the delta, sigma, beta and gamma amplitudes only during non-simultaneous NREM/REM sleep in the hippocampus. We demonstrated the brain structure-related and NREM/REM state-related heterogeneity of the motor cortical and hippocampal local sleep in control rats. The distinctly altered local NREM/REM states, alongside their episode dynamics and electroencephalographic (EEG) microstructures, suggest the importance of both the local neuronal network substrate and the NREM/REM neurochemical substrate in the control mechanisms of sleep.
PB  - Blackwell Publishing Ltd
T2  - Journal of Sleep Research
T1  - Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.
DO  - 10.1111/jsr.13090
SP  - e13090
ER  - 

@article{
author = "Petrović, Jelena and Radovanović, Ljiljana and Šaponjić, Jasna",
year = "2020",
abstract = "We investigated the homogeneity/heterogeneity of spontaneous sleep, simultaneously recorded in the motor cortex and the hippocampus of control rats, and particularly analysed simultaneous and non-simultaneous motor cortical and hippocampal non-rapid eye movement (NREM)/rapid eye movement (REM) sleep. We demonstrate that the sleep architectures of the motor cortex and hippocampus are different in control rats. There was an increase of NREM duration and a decrease of REM duration in the hippocampus versus the motor cortex. In terms of duration, NREM state is the most heterogeneous in the hippocampus, whereas the REM state is the most heterogeneous in the motor cortex. Whereas the hippocampal NREM duration was increased due to the prolongation of NREM episodes, the hippocampal REM duration decreased due to the decreased number of REM episodes. The heterogeneity of sleep in the motor cortex and hippocampus in control rats was particularly expressed through the inverse alteration of sigma amplitude during NREM sleep and beta/gamma amplitudes during REM sleep in the hippocampus, along with the delta, sigma, beta and gamma amplitudes only during non-simultaneous NREM/REM sleep in the hippocampus. We demonstrated the brain structure-related and NREM/REM state-related heterogeneity of the motor cortical and hippocampal local sleep in control rats. The distinctly altered local NREM/REM states, alongside their episode dynamics and electroencephalographic (EEG) microstructures, suggest the importance of both the local neuronal network substrate and the NREM/REM neurochemical substrate in the control mechanisms of sleep.",
publisher = "Blackwell Publishing Ltd",
journal = "Journal of Sleep Research",
title = "Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.",
doi = "10.1111/jsr.13090",
pages = "e13090"
}

Petrović, J., Radovanović, L.,& Šaponjić, J.. (2020). Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.. in Journal of Sleep Research
Blackwell Publishing Ltd., e13090.
https://doi.org/10.1111/jsr.13090

Petrović J, Radovanović L, Šaponjić J. Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.. in Journal of Sleep Research. 2020;:e13090.
doi:10.1111/jsr.13090 .

Petrović, Jelena, Radovanović, Ljiljana, Šaponjić, Jasna, "Diversity of simultaneous sleep in the motor cortex and hippocampus in rats." in Journal of Sleep Research (2020):e13090,
https://doi.org/10.1111/jsr.13090 . .

TY  - JOUR
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
AU  - Kapor, Slobodan
AU  - Perović, Milka
AU  - Petrović, Jelena
AU  - Pešić, Vesna
AU  - Kanazir, Selma
AU  - Šaponjić, Jasna
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0166432817312391
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29170000
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3361
AB  - In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.
T2  - Behavioural Brain Research
T1  - Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat
VL  - 339
DO  - 10.1016/j.bbr.2017.11.021
SP  - 79
EP  - 92
ER  - 

@article{
author = "Ćirić, Jelena and Lazić, Katarina and Kapor, Slobodan and Perović, Milka and Petrović, Jelena and Pešić, Vesna and Kanazir, Selma and Šaponjić, Jasna",
year = "2018",
abstract = "In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.",
journal = "Behavioural Brain Research",
title = "Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat",
volume = "339",
doi = "10.1016/j.bbr.2017.11.021",
pages = "79-92"
}

Ćirić, J., Lazić, K., Kapor, S., Perović, M., Petrović, J., Pešić, V., Kanazir, S.,& Šaponjić, J.. (2018). Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat. in Behavioural Brain Research, 339, 79-92.
https://doi.org/10.1016/j.bbr.2017.11.021

Ćirić J, Lazić K, Kapor S, Perović M, Petrović J, Pešić V, Kanazir S, Šaponjić J. Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat. in Behavioural Brain Research. 2018;339:79-92.
doi:10.1016/j.bbr.2017.11.021 .

Ćirić, Jelena, Lazić, Katarina, Kapor, Slobodan, Perović, Milka, Petrović, Jelena, Pešić, Vesna, Kanazir, Selma, Šaponjić, Jasna, "Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat" in Behavioural Brain Research, 339 (2018):79-92,
https://doi.org/10.1016/j.bbr.2017.11.021 . .

TY  - JOUR
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
AU  - Kapor, Slobodan
AU  - Perović, Milka
AU  - Petrović, Jelena
AU  - Pešić, Vesna
AU  - Kanazir, Selma
AU  - Šaponjić, Jasna
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0166432817312391
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29170000
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2932
AB  - In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.
T2  - Behavioural Brain Research
T1  - Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat
VL  - 339
DO  - 10.1016/j.bbr.2017.11.021
SP  - 79
EP  - 92
ER  - 

@article{
author = "Ćirić, Jelena and Lazić, Katarina and Kapor, Slobodan and Perović, Milka and Petrović, Jelena and Pešić, Vesna and Kanazir, Selma and Šaponjić, Jasna",
year = "2018",
abstract = "In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.",
journal = "Behavioural Brain Research",
title = "Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat",
volume = "339",
doi = "10.1016/j.bbr.2017.11.021",
pages = "79-92"
}

Ćirić, J., Lazić, K., Kapor, S., Perović, M., Petrović, J., Pešić, V., Kanazir, S.,& Šaponjić, J.. (2018). Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat. in Behavioural Brain Research, 339, 79-92.
https://doi.org/10.1016/j.bbr.2017.11.021

Ćirić J, Lazić K, Kapor S, Perović M, Petrović J, Pešić V, Kanazir S, Šaponjić J. Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat. in Behavioural Brain Research. 2018;339:79-92.
doi:10.1016/j.bbr.2017.11.021 .

Ćirić, Jelena, Lazić, Katarina, Kapor, Slobodan, Perović, Milka, Petrović, Jelena, Pešić, Vesna, Kanazir, Selma, Šaponjić, Jasna, "Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat" in Behavioural Brain Research, 339 (2018):79-92,
https://doi.org/10.1016/j.bbr.2017.11.021 . .

TY  - JOUR
AU  - Blagojević, Ana
AU  - Subakov Simić, Gordana
AU  - Ilić, Marija
AU  - Blaženčić, Jelena
AU  - Petrović, Jelena
AU  - Kostić, Dušan
AU  - Marjanović, Prvoslav
PY  - 2017
UR  - https://zenodo.org/record/454096#.WSbK7cb-uUk
UR  - http://botanicaserbica.bio.bg.ac.rs/2017_41_1.html#a682
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2747
AB  - The paper presents the first record of the freshwater red alga Paralemanea torulosa and new findings of the species Lemanea fluviatilis and Hildenbrandia rivularis in Serbia. The existence of all three species was recorded in the upper reaches of clean fast-flowing rivers and brooks belonging to the basin of the Danube River. Lemanea fluviatilis was found in the Dojkinacka River in Eastern Serbia, while Paralemanea torulosa was recorded in the Drina River and Hildenbrandia rivularis in the Cvetica Brook and Bioštanska Banja Brook in Western Serbia. These reports are important for conservation of the biodiversity of Serbia, since it is well known that freshwater red algae are endangered and rare species (taxa) in many countries. In Serbia they are under strict protection of the law.
T2  - Botanica Serbica
T1  - First record of Paralemanea torulosa (Roth) Sheath & A.R. Sherwood and new findings of Lemanea fluviatilis (Linnaeus) C. Ag. and Hildenbrandia rivularis (Liebmann) J. Agardh (Rhodophyta) in Serbia
IS  - 1
VL  - 41
DO  - 10.5281/zenodo.454096
SP  - 55
EP  - 63
ER  - 

@article{
author = "Blagojević, Ana and Subakov Simić, Gordana and Ilić, Marija and Blaženčić, Jelena and Petrović, Jelena and Kostić, Dušan and Marjanović, Prvoslav",
year = "2017",
abstract = "The paper presents the first record of the freshwater red alga Paralemanea torulosa and new findings of the species Lemanea fluviatilis and Hildenbrandia rivularis in Serbia. The existence of all three species was recorded in the upper reaches of clean fast-flowing rivers and brooks belonging to the basin of the Danube River. Lemanea fluviatilis was found in the Dojkinacka River in Eastern Serbia, while Paralemanea torulosa was recorded in the Drina River and Hildenbrandia rivularis in the Cvetica Brook and Bioštanska Banja Brook in Western Serbia. These reports are important for conservation of the biodiversity of Serbia, since it is well known that freshwater red algae are endangered and rare species (taxa) in many countries. In Serbia they are under strict protection of the law.",
journal = "Botanica Serbica",
title = "First record of Paralemanea torulosa (Roth) Sheath & A.R. Sherwood and new findings of Lemanea fluviatilis (Linnaeus) C. Ag. and Hildenbrandia rivularis (Liebmann) J. Agardh (Rhodophyta) in Serbia",
number = "1",
volume = "41",
doi = "10.5281/zenodo.454096",
pages = "55-63"
}

Blagojević, A., Subakov Simić, G., Ilić, M., Blaženčić, J., Petrović, J., Kostić, D.,& Marjanović, P.. (2017). First record of Paralemanea torulosa (Roth) Sheath & A.R. Sherwood and new findings of Lemanea fluviatilis (Linnaeus) C. Ag. and Hildenbrandia rivularis (Liebmann) J. Agardh (Rhodophyta) in Serbia. in Botanica Serbica, 41(1), 55-63.
https://doi.org/10.5281/zenodo.454096

Blagojević A, Subakov Simić G, Ilić M, Blaženčić J, Petrović J, Kostić D, Marjanović P. First record of Paralemanea torulosa (Roth) Sheath & A.R. Sherwood and new findings of Lemanea fluviatilis (Linnaeus) C. Ag. and Hildenbrandia rivularis (Liebmann) J. Agardh (Rhodophyta) in Serbia. in Botanica Serbica. 2017;41(1):55-63.
doi:10.5281/zenodo.454096 .

Blagojević, Ana, Subakov Simić, Gordana, Ilić, Marija, Blaženčić, Jelena, Petrović, Jelena, Kostić, Dušan, Marjanović, Prvoslav, "First record of Paralemanea torulosa (Roth) Sheath & A.R. Sherwood and new findings of Lemanea fluviatilis (Linnaeus) C. Ag. and Hildenbrandia rivularis (Liebmann) J. Agardh (Rhodophyta) in Serbia" in Botanica Serbica, 41, no. 1 (2017):55-63,
https://doi.org/10.5281/zenodo.454096 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Milosevic, Vuk
AU  - Živković, Miroslava
AU  - Stojanov, Dragan
AU  - Milojković, Olga
AU  - Kalauzi, Aleksandar
AU  - Šaponjić, Jasna
PY  - 2017
UR  - https://peerj.com/articles/3839
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2874
AB  - Background. We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. Methods. We included 10 patients with right middle cerebral artery (MCA) ischemic strokes a nd 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS), whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and MoCA memory index (MoCA-MIS). The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8), and corresponding lateral posterior (P3, P4, T5, T6) electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (α AVG), the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure), the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs). Statistical analysis was done using a Kruskal-Wallis ANOVA with a post-hoc Mann-WhitneyU two-tailed test, and Spearman's correlation. Results. We demonstrated transient cognitive impairment alongside a slower alpha fre- quency (αAVG) in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra- hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered "alpha flow", indicating the sustained augmentation of inter- hemispheric interactions. Although the stroke induced slower alpha was a transient phenomenon, the increased alpha intra-hemispheric synchronization, overlying the ipsi-lesional hemisphere, the increased alpha F3-F4 inter-hemispheric synchronization, the delayed alpha waves, and the newly established inter-hemispheric "alpha flow" within the frontal cortex, remained as a permanent consequence of the minor stroke. This newly established frontal inter-hemispheric "alpha flow" represented a permanent consequence of the ``hidden" stroke neuropathology, despite the fact that cognitive impairment has been returned to the control values. All the detected permanent changes at the EEG level with no cognitive impairment after a minor stroke could be a way for the brain to compensate for the lesion and restore the lost function. Discussion. Our study indicates slower EEG alpha generation, synchronization and ``flow" as potential biomarkers of cognitive impairment onset and/or compensatory post-stroke re-organizational processes.
T2  - PeerJ
T1  - Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke
IS  - 9
VL  - 5
DO  - 10.7717/peerj.3839
SP  - e3839
EP  - e3839
ER  - 

@article{
author = "Petrović, Jelena and Milosevic, Vuk and Živković, Miroslava and Stojanov, Dragan and Milojković, Olga and Kalauzi, Aleksandar and Šaponjić, Jasna",
year = "2017",
abstract = "Background. We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. Methods. We included 10 patients with right middle cerebral artery (MCA) ischemic strokes a nd 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS), whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and MoCA memory index (MoCA-MIS). The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8), and corresponding lateral posterior (P3, P4, T5, T6) electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (α AVG), the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure), the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs). Statistical analysis was done using a Kruskal-Wallis ANOVA with a post-hoc Mann-WhitneyU two-tailed test, and Spearman's correlation. Results. We demonstrated transient cognitive impairment alongside a slower alpha fre- quency (αAVG) in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra- hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered "alpha flow", indicating the sustained augmentation of inter- hemispheric interactions. Although the stroke induced slower alpha was a transient phenomenon, the increased alpha intra-hemispheric synchronization, overlying the ipsi-lesional hemisphere, the increased alpha F3-F4 inter-hemispheric synchronization, the delayed alpha waves, and the newly established inter-hemispheric "alpha flow" within the frontal cortex, remained as a permanent consequence of the minor stroke. This newly established frontal inter-hemispheric "alpha flow" represented a permanent consequence of the ``hidden" stroke neuropathology, despite the fact that cognitive impairment has been returned to the control values. All the detected permanent changes at the EEG level with no cognitive impairment after a minor stroke could be a way for the brain to compensate for the lesion and restore the lost function. Discussion. Our study indicates slower EEG alpha generation, synchronization and ``flow" as potential biomarkers of cognitive impairment onset and/or compensatory post-stroke re-organizational processes.",
journal = "PeerJ",
title = "Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke",
number = "9",
volume = "5",
doi = "10.7717/peerj.3839",
pages = "e3839-e3839"
}

Petrović, J., Milosevic, V., Živković, M., Stojanov, D., Milojković, O., Kalauzi, A.,& Šaponjić, J.. (2017). Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke. in PeerJ, 5(9), e3839-e3839.
https://doi.org/10.7717/peerj.3839

Petrović J, Milosevic V, Živković M, Stojanov D, Milojković O, Kalauzi A, Šaponjić J. Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke. in PeerJ. 2017;5(9):e3839-e3839.
doi:10.7717/peerj.3839 .

Petrović, Jelena, Milosevic, Vuk, Živković, Miroslava, Stojanov, Dragan, Milojković, Olga, Kalauzi, Aleksandar, Šaponjić, Jasna, "Slower EEG alpha generation, synchronization and “flow”—possible biomarkers of cognitive impairment and neuropathology of minor stroke" in PeerJ, 5, no. 9 (2017):e3839-e3839,
https://doi.org/10.7717/peerj.3839 . .

TY  - JOUR
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
AU  - Petrović, Jelena
AU  - Kalauzi, A
AU  - Šaponjić, Jasna
PY  - 2017
UR  - http://www.oatext.com/sleep-spindles-as-an-early-biomarker-of-rem-sleep-disorder-in-a-rat-model-of-parkinsons-disease-cholinopathy.php
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3296
AB  - Rhythmic oscillations of neuronal populations, generated by different mechanisms, are present at several levels of the central nervous system and serve many important physiological or reflect pathological functions. Understanding the role of brain oscillations as possible biomarkers of brain function and plasticity is still a challenge, and despite extensive research, their role is still not well established. We recently demonstrated that the hallmarks of earlier aging onset during impaired thalamo-cortical cholinergic innervation (in a rat model of Parkinson’s disease cholinopathy) were consistently expressed, from 3 and one half to 5 and one half months of age, through increased electroencephalographic (EEG) sigma activity amplitude during rapid eye movement (REM) sleep, as a unique aging induced REM sleep phenomenon. In addition, there was altered motor cortical drive during non-rapid-eye-movement (NREM) and REM sleep. In order to explain this new aging-induced REM sleep phenomenon, we analyzed possible differences between control REM sleep spindle activity and REM sleep spindle activity at the onset of REM sleep “enriched“ with sigma activity (at 4 and one half months of age), following bilateral pedunculopontine tegmental nucleus (PPT) cholinergic neuronal loss in the rat. We analzyed differences in spindle density, duration, and frequency. We demonstrated in young adult Wistar rats with the severely impaired PPT cholinergic innervation the alterations in sleep spindle dynamics and pattern during REM sleep in the motor cortex as the earliest biomarkers for the onset of their altered aging processes.
T2  - Translational Brain Rhythmicity
T1  - Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy
IS  - 1
VL  - 2
DO  - 10.15761/TBR.1000111
SP  - 1
EP  - 11
ER  - 

@article{
author = "Ćirić, Jelena and Lazić, Katarina and Petrović, Jelena and Kalauzi, A and Šaponjić, Jasna",
year = "2017",
abstract = "Rhythmic oscillations of neuronal populations, generated by different mechanisms, are present at several levels of the central nervous system and serve many important physiological or reflect pathological functions. Understanding the role of brain oscillations as possible biomarkers of brain function and plasticity is still a challenge, and despite extensive research, their role is still not well established. We recently demonstrated that the hallmarks of earlier aging onset during impaired thalamo-cortical cholinergic innervation (in a rat model of Parkinson’s disease cholinopathy) were consistently expressed, from 3 and one half to 5 and one half months of age, through increased electroencephalographic (EEG) sigma activity amplitude during rapid eye movement (REM) sleep, as a unique aging induced REM sleep phenomenon. In addition, there was altered motor cortical drive during non-rapid-eye-movement (NREM) and REM sleep. In order to explain this new aging-induced REM sleep phenomenon, we analyzed possible differences between control REM sleep spindle activity and REM sleep spindle activity at the onset of REM sleep “enriched“ with sigma activity (at 4 and one half months of age), following bilateral pedunculopontine tegmental nucleus (PPT) cholinergic neuronal loss in the rat. We analzyed differences in spindle density, duration, and frequency. We demonstrated in young adult Wistar rats with the severely impaired PPT cholinergic innervation the alterations in sleep spindle dynamics and pattern during REM sleep in the motor cortex as the earliest biomarkers for the onset of their altered aging processes.",
journal = "Translational Brain Rhythmicity",
title = "Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy",
number = "1",
volume = "2",
doi = "10.15761/TBR.1000111",
pages = "1-11"
}

Ćirić, J., Lazić, K., Petrović, J., Kalauzi, A.,& Šaponjić, J.. (2017). Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy. in Translational Brain Rhythmicity, 2(1), 1-11.
https://doi.org/10.15761/TBR.1000111

Ćirić J, Lazić K, Petrović J, Kalauzi A, Šaponjić J. Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy. in Translational Brain Rhythmicity. 2017;2(1):1-11.
doi:10.15761/TBR.1000111 .

Ćirić, Jelena, Lazić, Katarina, Petrović, Jelena, Kalauzi, A, Šaponjić, Jasna, "Sleep spindles as an early biomarker of REM sleep disorder in a rat model of Parkinson’s disease cholinopathy" in Translational Brain Rhythmicity, 2, no. 1 (2017):1-11,
https://doi.org/10.15761/TBR.1000111 . .

TY  - JOUR
AU  - Lazić, Katarina
AU  - Petrović, Jelena
AU  - Ćirić, Jelena
AU  - Kalauzi, Aleksandar
AU  - Šaponjić, Jasna
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0031938416306308
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3297
AB  - Postoperative sleep disorders, particularly the REM sleep disorder, may have a significant deleterious impact on postoperative outcomes and may contribute to the genesis of certain delayed postoperative complications. We have followed the effect of distinct anesthesia regimens (ketamine/diazepam vs. pentobarbital) over 6days following the induction of a stable anesthetized state in adult male Wistar rats, chronically instrumented for sleep recording. In order to compare the effect of both anesthetics in the physiological controls vs. the rats with impaired pedunculopontine tegmental nucleus (PPT) cholinergic innervation, during the operative procedure for the implantation of EEG and EMG electrodes, the bilateral PPT lesion was conducted using ibotenic acid (IBO). We have followed in particular post-anesthesia REM sleep. Our results show the distinct EEG microstructure of the motor cortex during the different stable anesthetized states, and their distinct impact on post-anesthesia REM sleep. In contrast to pentobarbital anesthesia, the ketamine/diazepam anesthesia potentiated the long-lasting post-anesthesia REM statewith higher muscle tone (REM1) vs. REM state with atonia (REM2). Whereas both anesthesias prolonged the post-anesthesia REM sleep duration, the long-term prolongation of the REM1 state was demonstrated only after the ketamine/diazepam anesthesia, first due to the increased number of REM1 episodes, and then due to the prolonged REM1 episodes duration. On the other hand, whereas both anesthetic regimens abolished the prolonged post-anesthesia REM/REM1 sleep and the EEG microstructure disorder during REM sleep, only the pentobarbital abolished the increased NREM/REM/NREM transitions, caused by the PPT lesion. In addition, in the PPT lesioned rats, the ketamine/diazepam anesthesia decreased the Wake/NREM/Wake transitions while the pentobarbital anesthesia decreased the Wake/REM/Wake transitions. Our present study suggests pentobarbital anesthesia as being highly beneficial for post-anesthesia REM sleep in the physiological condition as well as during PPT cholinergic neuropathology.
T2  - Physiology & Behavior
T1  - REM sleep disorder following general anesthesia in rats.
VL  - 168
DO  - 10.1016/j.physbeh.2016.10.013
SP  - 41
EP  - 54
ER  - 

@article{
author = "Lazić, Katarina and Petrović, Jelena and Ćirić, Jelena and Kalauzi, Aleksandar and Šaponjić, Jasna",
year = "2017",
abstract = "Postoperative sleep disorders, particularly the REM sleep disorder, may have a significant deleterious impact on postoperative outcomes and may contribute to the genesis of certain delayed postoperative complications. We have followed the effect of distinct anesthesia regimens (ketamine/diazepam vs. pentobarbital) over 6days following the induction of a stable anesthetized state in adult male Wistar rats, chronically instrumented for sleep recording. In order to compare the effect of both anesthetics in the physiological controls vs. the rats with impaired pedunculopontine tegmental nucleus (PPT) cholinergic innervation, during the operative procedure for the implantation of EEG and EMG electrodes, the bilateral PPT lesion was conducted using ibotenic acid (IBO). We have followed in particular post-anesthesia REM sleep. Our results show the distinct EEG microstructure of the motor cortex during the different stable anesthetized states, and their distinct impact on post-anesthesia REM sleep. In contrast to pentobarbital anesthesia, the ketamine/diazepam anesthesia potentiated the long-lasting post-anesthesia REM statewith higher muscle tone (REM1) vs. REM state with atonia (REM2). Whereas both anesthesias prolonged the post-anesthesia REM sleep duration, the long-term prolongation of the REM1 state was demonstrated only after the ketamine/diazepam anesthesia, first due to the increased number of REM1 episodes, and then due to the prolonged REM1 episodes duration. On the other hand, whereas both anesthetic regimens abolished the prolonged post-anesthesia REM/REM1 sleep and the EEG microstructure disorder during REM sleep, only the pentobarbital abolished the increased NREM/REM/NREM transitions, caused by the PPT lesion. In addition, in the PPT lesioned rats, the ketamine/diazepam anesthesia decreased the Wake/NREM/Wake transitions while the pentobarbital anesthesia decreased the Wake/REM/Wake transitions. Our present study suggests pentobarbital anesthesia as being highly beneficial for post-anesthesia REM sleep in the physiological condition as well as during PPT cholinergic neuropathology.",
journal = "Physiology & Behavior",
title = "REM sleep disorder following general anesthesia in rats.",
volume = "168",
doi = "10.1016/j.physbeh.2016.10.013",
pages = "41-54"
}

Lazić, K., Petrović, J., Ćirić, J., Kalauzi, A.,& Šaponjić, J.. (2017). REM sleep disorder following general anesthesia in rats.. in Physiology & Behavior, 168, 41-54.
https://doi.org/10.1016/j.physbeh.2016.10.013

Lazić K, Petrović J, Ćirić J, Kalauzi A, Šaponjić J. REM sleep disorder following general anesthesia in rats.. in Physiology & Behavior. 2017;168:41-54.
doi:10.1016/j.physbeh.2016.10.013 .

Lazić, Katarina, Petrović, Jelena, Ćirić, Jelena, Kalauzi, Aleksandar, Šaponjić, Jasna, "REM sleep disorder following general anesthesia in rats." in Physiology & Behavior, 168 (2017):41-54,
https://doi.org/10.1016/j.physbeh.2016.10.013 . .

TY  - CHAP
AU  - Šaponjić, Jasna
AU  - Petrović, Jelena
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
PY  - 2016
UR  - http://dx.doi.org/10.5772/62949
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2474
UR  - http://www.intechopen.com/books/challenges-in-parkinson-s-disease/disorders-of-sleep-and-motor-control-during-the-impaired-cholinergic-innervation-in-rat-relevance-to
AB  - The medical profession has been generally very slow to acknowledge the importance of sleep medicine and sleep research. Disorders of sleep are related to anxiety, many mental and neurodegenerative diseases, cardiovascular and respiratory disorders, and obesity. Our knowledge of the neural substrates of sleep/wake states and sleep-related behavior disorders regulation in health and the diseases, over more than 50 years of sleep research, is based on the experiments in animal models, pharmacotherapy, and the neuropathological studies in humans. But, we still need further work in fundamental multidisciplinary and clinical research between sleep and neurodegenerative disease investigators to understand normal and abnormal sleep, and to provide new insights into preventive or disease-altering approaches for therapy. Our aim is to give an overview of our recent results related to the importance of thalamo-cortical cholinergic brain system in the disorders of sleep and motor control during sleep, with particular relevance to Parkinson’s disease.
PB  - Rijeka: InTech
T2  - Challenges in Parkinson’s Disease
T1  - Disorders of Sleep and Motor Control During the Impaired Cholinergic Innervation in Rat – Relevance to Parkinson’s Disease
DO  - 10.5772/62949
SP  - 136
EP  - 153
ER  - 

@inbook{
author = "Šaponjić, Jasna and Petrović, Jelena and Ćirić, Jelena and Lazić, Katarina",
year = "2016",
abstract = "The medical profession has been generally very slow to acknowledge the importance of sleep medicine and sleep research. Disorders of sleep are related to anxiety, many mental and neurodegenerative diseases, cardiovascular and respiratory disorders, and obesity. Our knowledge of the neural substrates of sleep/wake states and sleep-related behavior disorders regulation in health and the diseases, over more than 50 years of sleep research, is based on the experiments in animal models, pharmacotherapy, and the neuropathological studies in humans. But, we still need further work in fundamental multidisciplinary and clinical research between sleep and neurodegenerative disease investigators to understand normal and abnormal sleep, and to provide new insights into preventive or disease-altering approaches for therapy. Our aim is to give an overview of our recent results related to the importance of thalamo-cortical cholinergic brain system in the disorders of sleep and motor control during sleep, with particular relevance to Parkinson’s disease.",
publisher = "Rijeka: InTech",
journal = "Challenges in Parkinson’s Disease",
booktitle = "Disorders of Sleep and Motor Control During the Impaired Cholinergic Innervation in Rat – Relevance to Parkinson’s Disease",
doi = "10.5772/62949",
pages = "136-153"
}

Šaponjić, J., Petrović, J., Ćirić, J.,& Lazić, K.. (2016). Disorders of Sleep and Motor Control During the Impaired Cholinergic Innervation in Rat – Relevance to Parkinson’s Disease. in Challenges in Parkinson’s Disease
Rijeka: InTech., 136-153.
https://doi.org/10.5772/62949

Šaponjić J, Petrović J, Ćirić J, Lazić K. Disorders of Sleep and Motor Control During the Impaired Cholinergic Innervation in Rat – Relevance to Parkinson’s Disease. in Challenges in Parkinson’s Disease. 2016;:136-153.
doi:10.5772/62949 .

Šaponjić, Jasna, Petrović, Jelena, Ćirić, Jelena, Lazić, Katarina, "Disorders of Sleep and Motor Control During the Impaired Cholinergic Innervation in Rat – Relevance to Parkinson’s Disease" in Challenges in Parkinson’s Disease (2016):136-153,
https://doi.org/10.5772/62949 . .

TY  - JOUR
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
AU  - Petrović, Jelena
AU  - Kalauzi, Aleksandar
AU  - Šaponjić, Jasna
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1909
UR  - http://www.sciencedirect.com/science/article/pii/S0166432815303454
AB  - We studied the impact of aging during sleep in the rat models of
   Alzheimer's (AD) and Parkinson's (PD) disease cholinergic neuropathology
   to determine the possible different and earlier onset of age-related
   sleep disorder during the neurodegenerative diseases vs. healthy aging.
   We used the bilateral nucleus basalis (NB) and pedunculopontine
   tegmental nucleus (PPT) lesioned rats as the in vivo models of
   functionally distinct cholinergic neuropathology, and we followed the
   impact of aging on sleep architecture, the electroencephalographic (EEG)
   microstructure and motor control across sleep/wake states.
   Our results have shown for the first time that the earliest signs of
   aging during distinct cholinergic neuropathology were expressed through
   a different and topographically specific EEG microstructure during rapid
   eye movement sleep (REM). EEG delta amplitude attenuation within the
   sensorimotor cortex (SMCx) during REM was the earliest sign of aging in
   the NB lesion. EEG sigma amplitude augmentation within the motor cortex
   (MCx) during REM was the earliest sign of aging in the PPT lesion. In
   addition, aging was differently expressed through the SMCx drive
   alterations, but it was commonly expressed through the MCx drive
   alterations during all sleep/wake states.
   Our study provided evidence of distinct REM sleep disorders and sleep
   state related cortical drives as the signs of aging onset during
   functionally distinct cholinergic neuropathologies (NB lesion vs. PPT
   lesion). (C) 2015 Elsevier B.V. All rights reserved.
T2  - Behavioural Brain Research
T1  - Age-related disorders of sleep and motor control in the rat models of
 functionally distinct cholinergic neuropathology
VL  - 301
DO  - 10.1016/j.bbr.2015.12.046
SP  - 273
EP  - 286
ER  - 

@article{
author = "Ćirić, Jelena and Lazić, Katarina and Petrović, Jelena and Kalauzi, Aleksandar and Šaponjić, Jasna",
year = "2016",
abstract = "We studied the impact of aging during sleep in the rat models of
   Alzheimer's (AD) and Parkinson's (PD) disease cholinergic neuropathology
   to determine the possible different and earlier onset of age-related
   sleep disorder during the neurodegenerative diseases vs. healthy aging.
   We used the bilateral nucleus basalis (NB) and pedunculopontine
   tegmental nucleus (PPT) lesioned rats as the in vivo models of
   functionally distinct cholinergic neuropathology, and we followed the
   impact of aging on sleep architecture, the electroencephalographic (EEG)
   microstructure and motor control across sleep/wake states.
   Our results have shown for the first time that the earliest signs of
   aging during distinct cholinergic neuropathology were expressed through
   a different and topographically specific EEG microstructure during rapid
   eye movement sleep (REM). EEG delta amplitude attenuation within the
   sensorimotor cortex (SMCx) during REM was the earliest sign of aging in
   the NB lesion. EEG sigma amplitude augmentation within the motor cortex
   (MCx) during REM was the earliest sign of aging in the PPT lesion. In
   addition, aging was differently expressed through the SMCx drive
   alterations, but it was commonly expressed through the MCx drive
   alterations during all sleep/wake states.
   Our study provided evidence of distinct REM sleep disorders and sleep
   state related cortical drives as the signs of aging onset during
   functionally distinct cholinergic neuropathologies (NB lesion vs. PPT
   lesion). (C) 2015 Elsevier B.V. All rights reserved.",
journal = "Behavioural Brain Research",
title = "Age-related disorders of sleep and motor control in the rat models of
 functionally distinct cholinergic neuropathology",
volume = "301",
doi = "10.1016/j.bbr.2015.12.046",
pages = "273-286"
}

Ćirić, J., Lazić, K., Petrović, J., Kalauzi, A.,& Šaponjić, J.. (2016). Age-related disorders of sleep and motor control in the rat models of
 functionally distinct cholinergic neuropathology. in Behavioural Brain Research, 301, 273-286.
https://doi.org/10.1016/j.bbr.2015.12.046

Ćirić J, Lazić K, Petrović J, Kalauzi A, Šaponjić J. Age-related disorders of sleep and motor control in the rat models of
 functionally distinct cholinergic neuropathology. in Behavioural Brain Research. 2016;301:273-286.
doi:10.1016/j.bbr.2015.12.046 .

Ćirić, Jelena, Lazić, Katarina, Petrović, Jelena, Kalauzi, Aleksandar, Šaponjić, Jasna, "Age-related disorders of sleep and motor control in the rat models of
 functionally distinct cholinergic neuropathology" in Behavioural Brain Research, 301 (2016):273-286,
https://doi.org/10.1016/j.bbr.2015.12.046 . .

TY  - THES
AU  - Petrović, Jelena
PY  - 2015
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=2924
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:11144/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=47560719
UR  - http://nardus.mpn.gov.rs/123456789/5447
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2434
AB  - Alchajmerova bolest (AB) i Parkinsonova bolest (PB) su najčešće neurodegenerativne bolesti starenja. Neuropatologija AB i PB podrazumeva selektivan gubitak specifičnih populacija neurona, uključujući i holinergičke neurone bazalnog prednjeg mozga i moždanog stabla, kao i ushodni obrazac progresije neurodegeneracije od struktura u moždanom stablu uključenih u regulaciju REM („rapid eye movement”) spavanja ka prednjemoždanim regionima. Poremećaji ponašanja u toku REM spavanja („REM sleep behavior disorders” – RBD) veoma često ostaju neprimećeni kod AB i PB pacijenata i mogu se javiti godinama pa čak i decenijama pre motornih i kognitivnih poremećaja. Ovo ukazuje na značaj istraživanja poremećaja ponašanja u toku REM spavanja kao mogućeg ranog znaka pojave najčešćih neurodegenerativnih bolesti starenja.
Predmet istraživanja ove doktorske disertacije bio je da u eksperimentalnim modelima AB i PB holinergičke neuropatologije po prvi put ispita uticaj unilateralnih i bilateralnih lezija glavnog izvora kortikalne holinergičke inervacije (nucleus basalis, NB jedro) i glavnog izvora talamo-kortikalne holinergičke inervacije (nucleus pedunculopontinus tegmentalis, PPT jedro) velikog mozga pacova na spavanje i elektroencefalografske (EEG) ritmove. U ovim eksperimentalnim modelima holinergičke neuropatologije humanih bolesti (NB i PPT lezije) unilateralne lezije su predstavljale lakše oblike ili početne stadijume neurodegeneracija, dok su bilateralne lezije predstavljale teže oblike ili kasnije stadijume neurodegeneracija, a sama progresija bolesti je praćena ukupno 5 nedelja zavisno od eksperimentalne grupe. 
U skladu sa osnovnom hipotezom ove doktorske disertacije, da funkcionalno različiti centralni holinergički sistemi imaju različite regulatorne funkcije u toku spavanja, koje se mogu definisati na osnovu EEG aktivnosti, postavljen je i osnovni cilj istraživanja: da se kroz analizu arhitekture spavanja, strukture prelaznih stanja i EEG mikrostrukture osnovnih faza u toku spavanja (budnost, NREM – „non rapid eye movement”, REM) u eksperimentalnim modelima funkcionalno različite holinergičke neuropatologije pronađu potencijalni EEG markeri početka, težine i progresije neurodegeneracije, sa mogućnošću dalje primene ovako senzitivnih metoda (definisanih EEG markera) u eventualnoj prevenciji i promeni terapijskog pristupa u pacijenata sa rizikom razvoja AB i PB.
Mužjaci pacova Wistar soja su hronično implantirani za registrovanje spavanja. U toku operativne procedure za implantaciju elektroda za elektroencefalografiju (EEG) i elektromiografiju (EMG), korišćenjem tehnike stereotaksički navođene mikroinfuzije ibotenične kiseline (ekscitotoksina koji je generalni glutamatergički agonista), izvšene su selektivne unilateralne ili bilateralne NB ili PPT lezije. 
Eksperimentalni protokol registrovanja spavanja je počinjao dve nedelje nakon oporavka od operativne procedure implantacije hroničnih elektroda, sa ili bez unilateralnih ili bilateralnih NB ili PPT lezija. Registrovano je 6 sati spavanja, jednom nedeljno tokom četiri nedelje u eksperimentima NB lezija, odnosno jednom nedeljno tokom pet nedelja u eksperimentima PPT lezija, korišćenjem programa DataWave SciWorks Experimenter 8.0 (Datawave Technologies, Longmont, SAD). 
Nakon završetka eksperimentalnog protokola registrovanja spavanja, NB i PPT lezije su identifikovane NADPH – diaforaza histohemijskim bojenjem, a zatim i kvantifikovane u celokupnoj antero-posteriornoj dimenziji strukture korišćenjem ImageJ 1.46 programa (NIH, SAD). 
Analiza spavanja i EEG signala urađena je, kako u kontrolnih pacova tako i u pacova sa identifikovanim NB ili PPT lezijama, u MATLAB 6.5 programu, korišćenjem originalno razvijenog programskog paketa. Na usnimljene šestočasovne signale je najpre primenjena Furijeova transformacija, a zatim je svaka od 2160 Furijeovih epoha dužine 10 s  diferencirana kao budnost, NREM ili REM faza spavanja. Pored toga, za potrebe detaljnije analize poremećaja REM faze spavanja izazvanih bilateralnom PPT lezijom, grupisanje REM epoha je na osnovu snage EMG-a dodatno razdvojeno na dva podgrupisanja REM1 (REM epohe sa većom snagom EMG-a, patološki REM) i REM2 (REM epohe sa manjom snagom EMG-a, fiziološki REM). Potom je korišćenjem EEG signala senzomotorne i motorne kore urađena topografska analiza arhitekture spavanja, strukture prelaznih stanja u toku spavanja, EEG mikrostrukture svih osnovnih faza u toku spavanja, kao i analiza kortiko-muskularih koherencija između EEG-a senzomotorne ili motorne kore velikog mozga i EMG-a mišića dorzalne vratne muskulature. Za izračunavanje grupne raspodele gustine verovatnoće relativnih amplituda svih budnost/NREM/REM/REM1/REM2 konvencionalnih EEG frekventnih opsega u toku 6 h spavanja korišćena je PDE („Probability Density Estimate”) funkcija u MATLAB 6.5 programu. U daljoj funkcionalnoj analizi poremećaja REM faze spavanja, za svaki od konvencionalnih EEG frekventnih opsega su korišćenjem „cohere” funkcije u MATLAB 6.5 izračunate REM/REM1/REM2 kortiko-muskularne koherencije između EEG-a senzomotorne ili motorne kore i EMG-a mišića dorzalne vratne muskulature. Za statističku obradu svih podataka korišćena je neparametarska jednofaktorska Kruskal-Wallis ANOVA sa post-hoc Mann-Whitney U kontrastnim testom.
Bilateralna NB lezija je privremeno promenila arhitekturu spavanja 14 dana nakon lezije. Iako u slučaju fiziološke kontrole nije bilo razlika u trajanju budnosti, NREM i REM faze spavanja između senzomotorne i motorne kore, bilateralna NB lezija je u senzomotornoj kori smanjila trajanje budnosti i povećala trajanje NREM faze spavanja, dok je u motornoj kori smanjila trajanje budnosti i povećala trajanje REM faze spavanja. Istovremeno, u svim eksperimentalnim grupama, kako u fiziološkoj kontroli, tako i u unilateralnoj i bilateralnoj NB leziji, je EEG teta amplituda budnosti, NREM i REM faze spavanja bila niža u motornoj u odnosu na senzomotornu koru. Pored toga, bilateralna NB lezija je u senzomotornoj kori izazvala povećanje REM teta amplitude u trajanju od tri nedelje, dok su u motornoj kori i unilateralna i bilateralna NB lezija izazvale povećanje teta amplitude i u budnosti i u REM fazi spavanja.
PPT lezija nije promenila arhitekturu spavanja, ali je značajno izmenila strukturu prelaznih stanja, kao i EEG mikrostrukturu svih osnovnih faza spavanja. Obe lezije, i unilateralna i bilateralna PPT lezija, su dugotrajno povećale broj budnost/REM i REM/budnost prelaza tokom celokunog perioda od 5 nedelja. Ova promena u strukturi prelaznih stanja je od 28. dana bila praćena smanjenjem broja NREM/REM i REM/NREM prelaza, ali samo nakon bilateralne PPT lezije, kao težeg oblika holinergičke neurodegeneracije. Unilateralna PPT lezija je izazvala povećanje EEG teta amplitude budnosti i EEG beta amplitude REM faze spavanja, a od treće nedelje nakon lezije i pad EEG delta amplitude budnosti. Bilateralna PPT lezija je izazvala povećanje EEG beta amplitude tokom svih faza spavanja, kao i povećanje EEG gama amplitude REM faze spavanja i smanjenje EEG delta amplitude budnosti i NREM faze spavanja.
Poređenje efekata bilateralne NB i bilateralne PPT lezije (modeli težih, odnosno progresivnijih oblika holinergičke neurodegeneracije) na arhitekturu spavanja, strukturu prelaznih stanja i EEG mikrostrukturu svih osnovnih faza spavanja je pokazalo postojanje topografski specifičnih razlika u poremećajima nastalim kao posledica degeneracije funkcionalno različitih holinergičkih inervacija velikog mozga pacova. Za razliku od bilateralne NB lezije koja je privremeno izmenila trajanje budnosti i NREM faze spavanja u senzomotornoj kori, odnosno trajanje budnosti i REM faze spavanja u motornoj kori, bilateralna PPT lezija nije izmenila arhitekturu spavanja. Bilateralna PPT lezija je u obe kore dugotrajno (tokom 4 nedelje) povećala broj budnost/REM i REM/budnost prelaza i ovaj porast je bio praćen nekonzistentnim promenama u broju NREM/REM i REM/NREM prelaza u senzomotornoj kori, a u motornoj kori povećanjem broja ovih prelaza. Bilateralna NB lezija je u senzomotornoj kori smanjila broj NREM/REM i REM/NREM prelaza, dok je u motornoj kori povećala broj ovih prelaza tokom četiri nedelje. Promene u EEG mikrostrukturi nakon  bilateralne PPT lezije bile su i u senzomotornoj i u motornoj kori izražene kao dugotrajno (tokom 4 nedelje) povećanje beta i gama amplitude budnosti, NREM i REM faze spavanja, odnosno kao smanjenje delta amplitude budnosti, ali samo u senzomotornoj kori. Nasuprot tome, bilateralna NB lezija je izazvala samo povećanje REM teta amplitude u senzomotornoj kori koje je trajalo tri nedelje. 
Pored promena u strukturi prelaznih stanja u toku spavanja i EEG mikrostrukturi svih osnovnih faza spavanja, bilateralna PPT lezija je dodatno uslovila izdvajanje dva funkcionalno različita REM stanja u okviru REM faze spavanja, REM1 (PPT lezijom prouzrokovan patološki REM, REM bez atonije, REM sigma koherencije) i REM2 (fiziološki REM, REM sa atonijom, REM teta koherencije), naročito u motornoj kori. Iako nije promenila arhitekturu spavanja senzomotorne kore, bilateralna PPT lezija je u motornoj kori produžila trajanje patološkog REM1 stanja, a povećala broj budnost/REM1/budnost i NREM/REM2/NREM prelaza u obe kore. U osnovi izmenjene REM EEG mikrostrukture su bile povećana beta amplituda senzomotorne kore za vreme celokupnog REM stanja i povećana teta amplituda motorne kore samo za vreme REM1 stanja. Bilateralna PPT lezija je izazvala generalizovan pad REM/REM1/REM2 beta kortiko-muskularne koherencije i dovela do izmene kontrole mišića dorzalne vratne muskulature dominantno iz senzomotorne kore. 
Ova doktorska disertacija je, koristeći po prvi put nov eksperimentalni model holinergičke PB neuropatologije (PPT lezija), stereotaksički navođenu mikroinfuziju kao nov metodološki pristup za selektivne lezije moždanih jedara, nov histohemijski metod identifikacije deficita holinergičkih neurona, nov pristup u kvantifikaciji neuronskog deficita, kao i nov način analize EEG signala za vreme različitih faza spavanja, po prvi put dokazala topografski specifične razlike u arhitekturi spavanja, strukturi prelaznih stanja i EEG mikrostrukturi osnovnih faza spavanja (budnost, NREM, REM), koje su nastale usled poremećaja funkcionalno različitih holinergičkih inervacija velikog mozga pacova (NB lezija u odnosu na PPT leziju). U ovom novom eksperimentalnom modelu holinergičke PB neuropatologije po prvi put su dokazani dugotrajni i veoma ozbiljni poremećaji u spavanju izraženi kao: povećanje broja budnost/REM i REM/budnost prelaza, povećana kortikalna aktivacija tokom svih osnovnih faza spavanja, izdvajanje dva različita REM stanja (pojava patološkog REM stanja pored fiziološkog REM stanja), kao i dominantna izmena kontrole mišića dorzalne vratne muskulature iz senzomotorne kore, iskazana kao pad REM/REM1/REM2 beta koherencije.
AB  - Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases of elderly. AD and PD neuropathology involves selective loss of specific neuronal population within the brain, including the basal forebrain and brainstem cholinergic neurons, with the ascending pattern of neurodegeneration progression from rapid eye movement (REM) sleep-related brainstem regulatory structures to the brain basal areas. REM sleep behavior disorders (RBD) very frequently go unnoticed in the AD and PD patients, and as a symptom, could precede the onset of motor and cognitive disturbances by years or even decades. This indicates the importance of RBD as a potential early marker of the neurodegenerative diseases of elderly.
Using the experimental models of AD and PD cholinergic neuropathology, this PhD thesis aimed to investigate for the first time the impact of unilateral and bilateral nucleus basalis (NB – the main source of cortical cholinergic innervation) and nucleus pedunculopontinus tegmentalis (PPT – the main source of thalamo-cortical cholinergic innervation) lesions on sleep and electroencephalographic (EEG) rhythms during sleep in rat. In these experimental models of cholinergic neuropathology (NB and PPT lesions) the unilateral lesions were used as the models of mild or early stage neurodegenerations, whereas the bilateral lesions were used as the models of severe or progressed neurodegenerations, and the follow up period was up to 5 weeks depending on the experimental group.
Based on the hypothesis that functionally distinct cholinergic systems have different regulatory functions during sleep, that could be defined by EEG activity, this study aimed to investigate the sleep/wake architecture, sleep/wake state-related transitions structure and EEG microstructure of three main brain states (Wake, NREM – non rapid eye movement, REM) in order to find the possible EEG markers for the onset, severity, and progression of the functionally distinct cholinergic innervations disorders. These EEG markers could be used as a sensitive and reliable methodology of early detection in the patients who are at risk to develop AD or PD, and for a potential prevention and modification of the therapeutic approach.
Male Wistar rats were chronically implanted for sleep recording. During operative procedure for the electroencephalographic (EEG) and electromyographic (EMG) electrodes implantation, the selective unilateral or bilateral NB or PPT lesions were performed by stereotaxically guided microinfusion of ibotenic acid (the general glutamate agonist).
Sleep recording sessions started after two weeks of recovery period. Sleep was recorded for 6 h, weekly, during 4 weeks in NB lesioned rats, and during 5 weeks in PPT lesioned rats, using DataWave SciWorks Experimenter 8.0 software (Datawave Technologies, Longmont, SAD).
At the end of recording sessions the NB and PPT lesions were identified by NADPH – diaphorase histochemistry, and quantified throughout the overall NB or PPT antero-posterior dimensions, using ImageJ 1.46 software (NIH, SAD).
Analysis of the signals recorded from the control rats and all rats with positively identified NB or PPT lesion was done in MATLAB 6.5 using originally developed software. Fourier analysis was applied on 6 h recordings, and each 10 s epoch was differentiated as Wake, NREM or REM state. Additionally, for detailed analysis of two distinct REM clusters, that emerged following bilateral PPT lesion, each REM epoch was further differentiated, based on the EMG power, as either REM without atonia (REM1, pathological REM), and REM with atonia (REM2, physiological REM). Further analysis included the topography of sleep/wake states architecture, sleep/wake state-related transitions structure, and EEG microstructure, as well as all REM related cortico-muscular coherences. To calculate the group probability density distribution of all conventional EEG frequency bands relative amplitudes/6 h for the Wake/NREM/REM/REM1/REM2 of each experimental group we used the Probability Density Estimate (PDE) routine within MATLAB 6.5. For the functional REM cluster differentiation the REM/REM1/REM2 cortico-muscular coherences (CMCs) were calculated separately, for each conventional EEG frequency band and each experimental group, between the EEG of sensorimotor or motor cortex and the EMG of the dorsal nuchal muscles using the MATLAB 6.5 cohere routine. All statistical analyses were done using Kruskal-Wallis ANOVA with post-hoc Mann-Whitney U two-tailed tests.
Bilateral NB lesion transiently altered sleep/wake states topography 14 days following lesion. While the control rats exhibited equivalent durations of Wake, NREM and REM, as determined by sensorimotor versus motor cortex EEG, the bilateral NB lesion decreased Wake duration in both cortices, with NREM duration increased within the sensorimotor cortex, and REM duration increased within the motor cortex. At the same time, Wake, NREM and REM theta relative amplitude was lower in motor versus sensorimotor cortex in all experimental groups. In sensorimotor cortex the bilateral NB lesion increased only REM theta amplitude for three weeks, whereas in motor cortex both Wake and REM theta amplitude were transiently increased 14 days following both the unilateral and bilateral NB lesion.
PPT lesion did not change the sleep/wake architecture but did change the sleep/wake state-related transitions structure and the Wake/NREM/REM EEG microstructures. Both the unilateral and bilateral PPT lesions sustainably increased Wake/REM and REM/Wake transitions during 5 weeks, followed by the decreased NREM/REM and REM/NREM transitions from 28 days only in the case of the bilateral PPT lesion, as a more severe cholinergic neurodegeneration. The unilateral PPT lesion augmented Wake theta and REM beta amplitude, and with a delay of one week it attenuated Wake delta amplitude. The bilateral PPT lesion augmented beta amplitude during all sleep states, and REM gamma amplitude, but simultaneously attenuated Wake and NREM delta amplitude.
Comparison of the bilateral NB versus bilateral PPT lesion (the models of severe or progressed cholinergic neurodegenerations) effects on the sleep/wake states architecture, sleep/wake state-related transitions structure and EEG microstructures indicated the topographically specific differentiation of functionally distinct cholinergic innervation disorders. Whereas the bilateral NB lesion transiently altered Wake/NREM duration within the sensorimotor cortex, and Wake/REM duration within the motor cortex, the bilateral PPT lesion did not change the sleep/wake states distributions. Bilateral PPT lesion sustainably (during 4 weeks) increased the Wake/REM and REM/Wake transitions within the both sensorimotor and motor cortex, followed by inconsistent dysregulation of the NREM/REM and REM/NREM transitions within the sensorimotor cortex, but oppositely by their increment within the motor cortex. Bilateral NB lesion sustainably (during 4 weeks) decreased the NREM/REM and REM/NREM transitions within the sensorimotor cortex, but oppositely increased them within the motor cortex. Sleep/wake state-related EEG microstructure following the bilateral PPT lesion was expressed as the sustained (during 4 weeks) Wake/NREM/REM beta and gamma amplitude augmentations within the both sensorimotor and motor cortex, and Wake delta amplitude attenuation, but only within the sensorimotor cortex. In contrast, the bilateral NB lesion augmented only REM theta amplitude within the sensorimotor cortex during three weeks.
Alongside the sleep/wake state-related transitions structure and Wake/NREM/REM EEG microstructure alteration, the bilateral PPT lesion in rats additionally potentiated the emergence of two distinct REM sleep states, REM1 (pathological REM, REM without atonia, sigma coherent REM) and REM2 (physiological REM, REM with atonia, theta coherent REM), specifically expressed within the motor cortex. Bilateral PPT lesion did not change the sleep/wake states architecture within the sensorimotor cortex, but pathologically increased the duration of REM1 within the motor cortex, alongside the increased Wake/REM1/Wake and NREM/REM2/NREM transitions within the both cortices. In addition, the augmented total REM beta amplitude within the sensorimotor cortex and REM1 theta amplitude within the motor cortex was the underlying EEG microstructure pathology. Finally, the bilateral PPT lesion dominantly induced sensorimotor cortex-dorsal nuchal muscle drive alteration, expressed throughout the REM/REM1/REM2 beta CMC decrease.
Introducing the novel experimental model of PD cholinergic neuropathology (PPT lesion), the stereotaxically guided microinfusion as a novel approach for the selective lesion of the brain nuclei, the novel histochemical method for the cholinergic neuronal loss identification, and the novel methodological approach for neuronal loss quantification, as well as the novel sleep-state related EEG signal analysis methodology, this PhD thesis evidenced for the first time the topographically different expression of the sleep/wake architecture, sleep/wake state-related transitions structure and Wake/NREM/REM EEG microstructure, induced by the functionally distinct cholinergic innervation disorders in rat (NB versus PPT lesion). This study demonstrated for the first time the PPT lesion (novel experimental model of PD cholinergic neuropathology) induced sustained and more severe sleep disturbances expressed as: the Wake/REM and REM/Wake transitions increase, augmented cortical activation across all sleep/wake states, potentiation of two distinct REM clusters, and dominant sensorimotor cortex-dorsal nuchal muscle drive alteration throughout the REM/REM1/REM2 beta CMC decrease.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Spavanje i elektroencefalografski ritmovi kao indikatori poremećaja funkcionalno različitih holinergičkih inervacija velikog mozga pacova
T1  - Sleep and electroencephalographic rhythms as an indicators of the functionally distinct cholinergic innervation disorders in rat brain
SP  - 1
EP  - 156
UR  - https://hdl.handle.net/21.15107/rcub_nardus_5447
ER  - 

@phdthesis{
author = "Petrović, Jelena",
year = "2015",
abstract = "Alchajmerova bolest (AB) i Parkinsonova bolest (PB) su najčešće neurodegenerativne bolesti starenja. Neuropatologija AB i PB podrazumeva selektivan gubitak specifičnih populacija neurona, uključujući i holinergičke neurone bazalnog prednjeg mozga i moždanog stabla, kao i ushodni obrazac progresije neurodegeneracije od struktura u moždanom stablu uključenih u regulaciju REM („rapid eye movement”) spavanja ka prednjemoždanim regionima. Poremećaji ponašanja u toku REM spavanja („REM sleep behavior disorders” – RBD) veoma često ostaju neprimećeni kod AB i PB pacijenata i mogu se javiti godinama pa čak i decenijama pre motornih i kognitivnih poremećaja. Ovo ukazuje na značaj istraživanja poremećaja ponašanja u toku REM spavanja kao mogućeg ranog znaka pojave najčešćih neurodegenerativnih bolesti starenja.
Predmet istraživanja ove doktorske disertacije bio je da u eksperimentalnim modelima AB i PB holinergičke neuropatologije po prvi put ispita uticaj unilateralnih i bilateralnih lezija glavnog izvora kortikalne holinergičke inervacije (nucleus basalis, NB jedro) i glavnog izvora talamo-kortikalne holinergičke inervacije (nucleus pedunculopontinus tegmentalis, PPT jedro) velikog mozga pacova na spavanje i elektroencefalografske (EEG) ritmove. U ovim eksperimentalnim modelima holinergičke neuropatologije humanih bolesti (NB i PPT lezije) unilateralne lezije su predstavljale lakše oblike ili početne stadijume neurodegeneracija, dok su bilateralne lezije predstavljale teže oblike ili kasnije stadijume neurodegeneracija, a sama progresija bolesti je praćena ukupno 5 nedelja zavisno od eksperimentalne grupe. 
U skladu sa osnovnom hipotezom ove doktorske disertacije, da funkcionalno različiti centralni holinergički sistemi imaju različite regulatorne funkcije u toku spavanja, koje se mogu definisati na osnovu EEG aktivnosti, postavljen je i osnovni cilj istraživanja: da se kroz analizu arhitekture spavanja, strukture prelaznih stanja i EEG mikrostrukture osnovnih faza u toku spavanja (budnost, NREM – „non rapid eye movement”, REM) u eksperimentalnim modelima funkcionalno različite holinergičke neuropatologije pronađu potencijalni EEG markeri početka, težine i progresije neurodegeneracije, sa mogućnošću dalje primene ovako senzitivnih metoda (definisanih EEG markera) u eventualnoj prevenciji i promeni terapijskog pristupa u pacijenata sa rizikom razvoja AB i PB.
Mužjaci pacova Wistar soja su hronično implantirani za registrovanje spavanja. U toku operativne procedure za implantaciju elektroda za elektroencefalografiju (EEG) i elektromiografiju (EMG), korišćenjem tehnike stereotaksički navođene mikroinfuzije ibotenične kiseline (ekscitotoksina koji je generalni glutamatergički agonista), izvšene su selektivne unilateralne ili bilateralne NB ili PPT lezije. 
Eksperimentalni protokol registrovanja spavanja je počinjao dve nedelje nakon oporavka od operativne procedure implantacije hroničnih elektroda, sa ili bez unilateralnih ili bilateralnih NB ili PPT lezija. Registrovano je 6 sati spavanja, jednom nedeljno tokom četiri nedelje u eksperimentima NB lezija, odnosno jednom nedeljno tokom pet nedelja u eksperimentima PPT lezija, korišćenjem programa DataWave SciWorks Experimenter 8.0 (Datawave Technologies, Longmont, SAD). 
Nakon završetka eksperimentalnog protokola registrovanja spavanja, NB i PPT lezije su identifikovane NADPH – diaforaza histohemijskim bojenjem, a zatim i kvantifikovane u celokupnoj antero-posteriornoj dimenziji strukture korišćenjem ImageJ 1.46 programa (NIH, SAD). 
Analiza spavanja i EEG signala urađena je, kako u kontrolnih pacova tako i u pacova sa identifikovanim NB ili PPT lezijama, u MATLAB 6.5 programu, korišćenjem originalno razvijenog programskog paketa. Na usnimljene šestočasovne signale je najpre primenjena Furijeova transformacija, a zatim je svaka od 2160 Furijeovih epoha dužine 10 s  diferencirana kao budnost, NREM ili REM faza spavanja. Pored toga, za potrebe detaljnije analize poremećaja REM faze spavanja izazvanih bilateralnom PPT lezijom, grupisanje REM epoha je na osnovu snage EMG-a dodatno razdvojeno na dva podgrupisanja REM1 (REM epohe sa većom snagom EMG-a, patološki REM) i REM2 (REM epohe sa manjom snagom EMG-a, fiziološki REM). Potom je korišćenjem EEG signala senzomotorne i motorne kore urađena topografska analiza arhitekture spavanja, strukture prelaznih stanja u toku spavanja, EEG mikrostrukture svih osnovnih faza u toku spavanja, kao i analiza kortiko-muskularih koherencija između EEG-a senzomotorne ili motorne kore velikog mozga i EMG-a mišića dorzalne vratne muskulature. Za izračunavanje grupne raspodele gustine verovatnoće relativnih amplituda svih budnost/NREM/REM/REM1/REM2 konvencionalnih EEG frekventnih opsega u toku 6 h spavanja korišćena je PDE („Probability Density Estimate”) funkcija u MATLAB 6.5 programu. U daljoj funkcionalnoj analizi poremećaja REM faze spavanja, za svaki od konvencionalnih EEG frekventnih opsega su korišćenjem „cohere” funkcije u MATLAB 6.5 izračunate REM/REM1/REM2 kortiko-muskularne koherencije između EEG-a senzomotorne ili motorne kore i EMG-a mišića dorzalne vratne muskulature. Za statističku obradu svih podataka korišćena je neparametarska jednofaktorska Kruskal-Wallis ANOVA sa post-hoc Mann-Whitney U kontrastnim testom.
Bilateralna NB lezija je privremeno promenila arhitekturu spavanja 14 dana nakon lezije. Iako u slučaju fiziološke kontrole nije bilo razlika u trajanju budnosti, NREM i REM faze spavanja između senzomotorne i motorne kore, bilateralna NB lezija je u senzomotornoj kori smanjila trajanje budnosti i povećala trajanje NREM faze spavanja, dok je u motornoj kori smanjila trajanje budnosti i povećala trajanje REM faze spavanja. Istovremeno, u svim eksperimentalnim grupama, kako u fiziološkoj kontroli, tako i u unilateralnoj i bilateralnoj NB leziji, je EEG teta amplituda budnosti, NREM i REM faze spavanja bila niža u motornoj u odnosu na senzomotornu koru. Pored toga, bilateralna NB lezija je u senzomotornoj kori izazvala povećanje REM teta amplitude u trajanju od tri nedelje, dok su u motornoj kori i unilateralna i bilateralna NB lezija izazvale povećanje teta amplitude i u budnosti i u REM fazi spavanja.
PPT lezija nije promenila arhitekturu spavanja, ali je značajno izmenila strukturu prelaznih stanja, kao i EEG mikrostrukturu svih osnovnih faza spavanja. Obe lezije, i unilateralna i bilateralna PPT lezija, su dugotrajno povećale broj budnost/REM i REM/budnost prelaza tokom celokunog perioda od 5 nedelja. Ova promena u strukturi prelaznih stanja je od 28. dana bila praćena smanjenjem broja NREM/REM i REM/NREM prelaza, ali samo nakon bilateralne PPT lezije, kao težeg oblika holinergičke neurodegeneracije. Unilateralna PPT lezija je izazvala povećanje EEG teta amplitude budnosti i EEG beta amplitude REM faze spavanja, a od treće nedelje nakon lezije i pad EEG delta amplitude budnosti. Bilateralna PPT lezija je izazvala povećanje EEG beta amplitude tokom svih faza spavanja, kao i povećanje EEG gama amplitude REM faze spavanja i smanjenje EEG delta amplitude budnosti i NREM faze spavanja.
Poređenje efekata bilateralne NB i bilateralne PPT lezije (modeli težih, odnosno progresivnijih oblika holinergičke neurodegeneracije) na arhitekturu spavanja, strukturu prelaznih stanja i EEG mikrostrukturu svih osnovnih faza spavanja je pokazalo postojanje topografski specifičnih razlika u poremećajima nastalim kao posledica degeneracije funkcionalno različitih holinergičkih inervacija velikog mozga pacova. Za razliku od bilateralne NB lezije koja je privremeno izmenila trajanje budnosti i NREM faze spavanja u senzomotornoj kori, odnosno trajanje budnosti i REM faze spavanja u motornoj kori, bilateralna PPT lezija nije izmenila arhitekturu spavanja. Bilateralna PPT lezija je u obe kore dugotrajno (tokom 4 nedelje) povećala broj budnost/REM i REM/budnost prelaza i ovaj porast je bio praćen nekonzistentnim promenama u broju NREM/REM i REM/NREM prelaza u senzomotornoj kori, a u motornoj kori povećanjem broja ovih prelaza. Bilateralna NB lezija je u senzomotornoj kori smanjila broj NREM/REM i REM/NREM prelaza, dok je u motornoj kori povećala broj ovih prelaza tokom četiri nedelje. Promene u EEG mikrostrukturi nakon  bilateralne PPT lezije bile su i u senzomotornoj i u motornoj kori izražene kao dugotrajno (tokom 4 nedelje) povećanje beta i gama amplitude budnosti, NREM i REM faze spavanja, odnosno kao smanjenje delta amplitude budnosti, ali samo u senzomotornoj kori. Nasuprot tome, bilateralna NB lezija je izazvala samo povećanje REM teta amplitude u senzomotornoj kori koje je trajalo tri nedelje. 
Pored promena u strukturi prelaznih stanja u toku spavanja i EEG mikrostrukturi svih osnovnih faza spavanja, bilateralna PPT lezija je dodatno uslovila izdvajanje dva funkcionalno različita REM stanja u okviru REM faze spavanja, REM1 (PPT lezijom prouzrokovan patološki REM, REM bez atonije, REM sigma koherencije) i REM2 (fiziološki REM, REM sa atonijom, REM teta koherencije), naročito u motornoj kori. Iako nije promenila arhitekturu spavanja senzomotorne kore, bilateralna PPT lezija je u motornoj kori produžila trajanje patološkog REM1 stanja, a povećala broj budnost/REM1/budnost i NREM/REM2/NREM prelaza u obe kore. U osnovi izmenjene REM EEG mikrostrukture su bile povećana beta amplituda senzomotorne kore za vreme celokupnog REM stanja i povećana teta amplituda motorne kore samo za vreme REM1 stanja. Bilateralna PPT lezija je izazvala generalizovan pad REM/REM1/REM2 beta kortiko-muskularne koherencije i dovela do izmene kontrole mišića dorzalne vratne muskulature dominantno iz senzomotorne kore. 
Ova doktorska disertacija je, koristeći po prvi put nov eksperimentalni model holinergičke PB neuropatologije (PPT lezija), stereotaksički navođenu mikroinfuziju kao nov metodološki pristup za selektivne lezije moždanih jedara, nov histohemijski metod identifikacije deficita holinergičkih neurona, nov pristup u kvantifikaciji neuronskog deficita, kao i nov način analize EEG signala za vreme različitih faza spavanja, po prvi put dokazala topografski specifične razlike u arhitekturi spavanja, strukturi prelaznih stanja i EEG mikrostrukturi osnovnih faza spavanja (budnost, NREM, REM), koje su nastale usled poremećaja funkcionalno različitih holinergičkih inervacija velikog mozga pacova (NB lezija u odnosu na PPT leziju). U ovom novom eksperimentalnom modelu holinergičke PB neuropatologije po prvi put su dokazani dugotrajni i veoma ozbiljni poremećaji u spavanju izraženi kao: povećanje broja budnost/REM i REM/budnost prelaza, povećana kortikalna aktivacija tokom svih osnovnih faza spavanja, izdvajanje dva različita REM stanja (pojava patološkog REM stanja pored fiziološkog REM stanja), kao i dominantna izmena kontrole mišića dorzalne vratne muskulature iz senzomotorne kore, iskazana kao pad REM/REM1/REM2 beta koherencije., Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases of elderly. AD and PD neuropathology involves selective loss of specific neuronal population within the brain, including the basal forebrain and brainstem cholinergic neurons, with the ascending pattern of neurodegeneration progression from rapid eye movement (REM) sleep-related brainstem regulatory structures to the brain basal areas. REM sleep behavior disorders (RBD) very frequently go unnoticed in the AD and PD patients, and as a symptom, could precede the onset of motor and cognitive disturbances by years or even decades. This indicates the importance of RBD as a potential early marker of the neurodegenerative diseases of elderly.
Using the experimental models of AD and PD cholinergic neuropathology, this PhD thesis aimed to investigate for the first time the impact of unilateral and bilateral nucleus basalis (NB – the main source of cortical cholinergic innervation) and nucleus pedunculopontinus tegmentalis (PPT – the main source of thalamo-cortical cholinergic innervation) lesions on sleep and electroencephalographic (EEG) rhythms during sleep in rat. In these experimental models of cholinergic neuropathology (NB and PPT lesions) the unilateral lesions were used as the models of mild or early stage neurodegenerations, whereas the bilateral lesions were used as the models of severe or progressed neurodegenerations, and the follow up period was up to 5 weeks depending on the experimental group.
Based on the hypothesis that functionally distinct cholinergic systems have different regulatory functions during sleep, that could be defined by EEG activity, this study aimed to investigate the sleep/wake architecture, sleep/wake state-related transitions structure and EEG microstructure of three main brain states (Wake, NREM – non rapid eye movement, REM) in order to find the possible EEG markers for the onset, severity, and progression of the functionally distinct cholinergic innervations disorders. These EEG markers could be used as a sensitive and reliable methodology of early detection in the patients who are at risk to develop AD or PD, and for a potential prevention and modification of the therapeutic approach.
Male Wistar rats were chronically implanted for sleep recording. During operative procedure for the electroencephalographic (EEG) and electromyographic (EMG) electrodes implantation, the selective unilateral or bilateral NB or PPT lesions were performed by stereotaxically guided microinfusion of ibotenic acid (the general glutamate agonist).
Sleep recording sessions started after two weeks of recovery period. Sleep was recorded for 6 h, weekly, during 4 weeks in NB lesioned rats, and during 5 weeks in PPT lesioned rats, using DataWave SciWorks Experimenter 8.0 software (Datawave Technologies, Longmont, SAD).
At the end of recording sessions the NB and PPT lesions were identified by NADPH – diaphorase histochemistry, and quantified throughout the overall NB or PPT antero-posterior dimensions, using ImageJ 1.46 software (NIH, SAD).
Analysis of the signals recorded from the control rats and all rats with positively identified NB or PPT lesion was done in MATLAB 6.5 using originally developed software. Fourier analysis was applied on 6 h recordings, and each 10 s epoch was differentiated as Wake, NREM or REM state. Additionally, for detailed analysis of two distinct REM clusters, that emerged following bilateral PPT lesion, each REM epoch was further differentiated, based on the EMG power, as either REM without atonia (REM1, pathological REM), and REM with atonia (REM2, physiological REM). Further analysis included the topography of sleep/wake states architecture, sleep/wake state-related transitions structure, and EEG microstructure, as well as all REM related cortico-muscular coherences. To calculate the group probability density distribution of all conventional EEG frequency bands relative amplitudes/6 h for the Wake/NREM/REM/REM1/REM2 of each experimental group we used the Probability Density Estimate (PDE) routine within MATLAB 6.5. For the functional REM cluster differentiation the REM/REM1/REM2 cortico-muscular coherences (CMCs) were calculated separately, for each conventional EEG frequency band and each experimental group, between the EEG of sensorimotor or motor cortex and the EMG of the dorsal nuchal muscles using the MATLAB 6.5 cohere routine. All statistical analyses were done using Kruskal-Wallis ANOVA with post-hoc Mann-Whitney U two-tailed tests.
Bilateral NB lesion transiently altered sleep/wake states topography 14 days following lesion. While the control rats exhibited equivalent durations of Wake, NREM and REM, as determined by sensorimotor versus motor cortex EEG, the bilateral NB lesion decreased Wake duration in both cortices, with NREM duration increased within the sensorimotor cortex, and REM duration increased within the motor cortex. At the same time, Wake, NREM and REM theta relative amplitude was lower in motor versus sensorimotor cortex in all experimental groups. In sensorimotor cortex the bilateral NB lesion increased only REM theta amplitude for three weeks, whereas in motor cortex both Wake and REM theta amplitude were transiently increased 14 days following both the unilateral and bilateral NB lesion.
PPT lesion did not change the sleep/wake architecture but did change the sleep/wake state-related transitions structure and the Wake/NREM/REM EEG microstructures. Both the unilateral and bilateral PPT lesions sustainably increased Wake/REM and REM/Wake transitions during 5 weeks, followed by the decreased NREM/REM and REM/NREM transitions from 28 days only in the case of the bilateral PPT lesion, as a more severe cholinergic neurodegeneration. The unilateral PPT lesion augmented Wake theta and REM beta amplitude, and with a delay of one week it attenuated Wake delta amplitude. The bilateral PPT lesion augmented beta amplitude during all sleep states, and REM gamma amplitude, but simultaneously attenuated Wake and NREM delta amplitude.
Comparison of the bilateral NB versus bilateral PPT lesion (the models of severe or progressed cholinergic neurodegenerations) effects on the sleep/wake states architecture, sleep/wake state-related transitions structure and EEG microstructures indicated the topographically specific differentiation of functionally distinct cholinergic innervation disorders. Whereas the bilateral NB lesion transiently altered Wake/NREM duration within the sensorimotor cortex, and Wake/REM duration within the motor cortex, the bilateral PPT lesion did not change the sleep/wake states distributions. Bilateral PPT lesion sustainably (during 4 weeks) increased the Wake/REM and REM/Wake transitions within the both sensorimotor and motor cortex, followed by inconsistent dysregulation of the NREM/REM and REM/NREM transitions within the sensorimotor cortex, but oppositely by their increment within the motor cortex. Bilateral NB lesion sustainably (during 4 weeks) decreased the NREM/REM and REM/NREM transitions within the sensorimotor cortex, but oppositely increased them within the motor cortex. Sleep/wake state-related EEG microstructure following the bilateral PPT lesion was expressed as the sustained (during 4 weeks) Wake/NREM/REM beta and gamma amplitude augmentations within the both sensorimotor and motor cortex, and Wake delta amplitude attenuation, but only within the sensorimotor cortex. In contrast, the bilateral NB lesion augmented only REM theta amplitude within the sensorimotor cortex during three weeks.
Alongside the sleep/wake state-related transitions structure and Wake/NREM/REM EEG microstructure alteration, the bilateral PPT lesion in rats additionally potentiated the emergence of two distinct REM sleep states, REM1 (pathological REM, REM without atonia, sigma coherent REM) and REM2 (physiological REM, REM with atonia, theta coherent REM), specifically expressed within the motor cortex. Bilateral PPT lesion did not change the sleep/wake states architecture within the sensorimotor cortex, but pathologically increased the duration of REM1 within the motor cortex, alongside the increased Wake/REM1/Wake and NREM/REM2/NREM transitions within the both cortices. In addition, the augmented total REM beta amplitude within the sensorimotor cortex and REM1 theta amplitude within the motor cortex was the underlying EEG microstructure pathology. Finally, the bilateral PPT lesion dominantly induced sensorimotor cortex-dorsal nuchal muscle drive alteration, expressed throughout the REM/REM1/REM2 beta CMC decrease.
Introducing the novel experimental model of PD cholinergic neuropathology (PPT lesion), the stereotaxically guided microinfusion as a novel approach for the selective lesion of the brain nuclei, the novel histochemical method for the cholinergic neuronal loss identification, and the novel methodological approach for neuronal loss quantification, as well as the novel sleep-state related EEG signal analysis methodology, this PhD thesis evidenced for the first time the topographically different expression of the sleep/wake architecture, sleep/wake state-related transitions structure and Wake/NREM/REM EEG microstructure, induced by the functionally distinct cholinergic innervation disorders in rat (NB versus PPT lesion). This study demonstrated for the first time the PPT lesion (novel experimental model of PD cholinergic neuropathology) induced sustained and more severe sleep disturbances expressed as: the Wake/REM and REM/Wake transitions increase, augmented cortical activation across all sleep/wake states, potentiation of two distinct REM clusters, and dominant sensorimotor cortex-dorsal nuchal muscle drive alteration throughout the REM/REM1/REM2 beta CMC decrease.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Spavanje i elektroencefalografski ritmovi kao indikatori poremećaja funkcionalno različitih holinergičkih inervacija velikog mozga pacova, Sleep and electroencephalographic rhythms as an indicators of the functionally distinct cholinergic innervation disorders in rat brain",
pages = "1-156",
url = "https://hdl.handle.net/21.15107/rcub_nardus_5447"
}

Petrović, J.. (2015). Spavanje i elektroencefalografski ritmovi kao indikatori poremećaja funkcionalno različitih holinergičkih inervacija velikog mozga pacova. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-156.
https://hdl.handle.net/21.15107/rcub_nardus_5447

Petrović J. Spavanje i elektroencefalografski ritmovi kao indikatori poremećaja funkcionalno različitih holinergičkih inervacija velikog mozga pacova. in University of Belgrade, Faculty of Biology. 2015;:1-156.
https://hdl.handle.net/21.15107/rcub_nardus_5447 .

Petrović, Jelena, "Spavanje i elektroencefalografski ritmovi kao indikatori poremećaja funkcionalno različitih holinergičkih inervacija velikog mozga pacova" in University of Belgrade, Faculty of Biology (2015):1-156,
https://hdl.handle.net/21.15107/rcub_nardus_5447 .

TY  - JOUR
AU  - Šaponjić, Jasna
AU  - Petrović, Jelena
AU  - Kalauzi, Aleksandar
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
AU  - Radulovacki, Miodrag
AU  - Carley, David W
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1027
AB  - We examined the effects of unilateral and bilateral nucleus basalis (NB) lesion in rat on sleep/wake states, and sleep/wake state-related electroencephalographic (EEG) frequency relative amplitude distributions. We aimed this study to identify the possible EEG markers for the onset and progression of cortical cholinergic neurodegeneration in rats. NB lesion was performed by ibotenic acid (IBO) microinfusion, and identified by NADPH-diaphorase histochemistry. Sleep/wake states related EEG relative amplitude analysis was done using the Probability Density Estimate (PDE) routine supplied with MATLAB 6.5. Bilateral NB lesion transiently altered gross sleep/wake states topography 14 days following lesion. While control rats exhibited equivalent durations of Wake, NREM and REM, as determined by sensorimotor versus motor cortex EEG, bilateral NB lesion decreased Wake duration in both cortices, with NREM duration increased within sensorimotor cortex, and REM duration increased within motor cortex. Also, Wake, NREM and REM theta relative amplitude was lower in motor versus sensorimotor cortex in all groups of animals. In sensorimotor cortex bilateral NB lesion increased only REM theta relative amplitude from 1421 days following lesion, and returned to control value 28 days following lesion. In motor cortex both Wake and REM theta relative amplitude transiently increased 14 days following unilateral and bilateral NB lesion, and returned to control values 21 days after lesions. We demonstrated at functional level, for the first time, the topographically specific impact of NB cholinergic cortical afferent system dysregulation on sleep/wake states, REM and Wake EEG theta relative amplitude.
T2  - Sleep and Biological Rhythms
T1  - Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder
IS  - 2
VL  - 11
SP  - 243
EP  - 115
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1027
ER  - 

@article{
author = "Šaponjić, Jasna and Petrović, Jelena and Kalauzi, Aleksandar and Ćirić, Jelena and Lazić, Katarina and Radulovacki, Miodrag and Carley, David W",
year = "2013",
abstract = "We examined the effects of unilateral and bilateral nucleus basalis (NB) lesion in rat on sleep/wake states, and sleep/wake state-related electroencephalographic (EEG) frequency relative amplitude distributions. We aimed this study to identify the possible EEG markers for the onset and progression of cortical cholinergic neurodegeneration in rats. NB lesion was performed by ibotenic acid (IBO) microinfusion, and identified by NADPH-diaphorase histochemistry. Sleep/wake states related EEG relative amplitude analysis was done using the Probability Density Estimate (PDE) routine supplied with MATLAB 6.5. Bilateral NB lesion transiently altered gross sleep/wake states topography 14 days following lesion. While control rats exhibited equivalent durations of Wake, NREM and REM, as determined by sensorimotor versus motor cortex EEG, bilateral NB lesion decreased Wake duration in both cortices, with NREM duration increased within sensorimotor cortex, and REM duration increased within motor cortex. Also, Wake, NREM and REM theta relative amplitude was lower in motor versus sensorimotor cortex in all groups of animals. In sensorimotor cortex bilateral NB lesion increased only REM theta relative amplitude from 1421 days following lesion, and returned to control value 28 days following lesion. In motor cortex both Wake and REM theta relative amplitude transiently increased 14 days following unilateral and bilateral NB lesion, and returned to control values 21 days after lesions. We demonstrated at functional level, for the first time, the topographically specific impact of NB cholinergic cortical afferent system dysregulation on sleep/wake states, REM and Wake EEG theta relative amplitude.",
journal = "Sleep and Biological Rhythms",
title = "Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder",
number = "2",
volume = "11",
pages = "243-115",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1027"
}

Šaponjić, J., Petrović, J., Kalauzi, A., Ćirić, J., Lazić, K., Radulovacki, M.,& Carley, D. W.. (2013). Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder. in Sleep and Biological Rhythms, 11(2), 243-115.
https://hdl.handle.net/21.15107/rcub_ibiss_1027

Šaponjić J, Petrović J, Kalauzi A, Ćirić J, Lazić K, Radulovacki M, Carley DW. Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder. in Sleep and Biological Rhythms. 2013;11(2):243-115.
https://hdl.handle.net/21.15107/rcub_ibiss_1027 .

Šaponjić, Jasna, Petrović, Jelena, Kalauzi, Aleksandar, Ćirić, Jelena, Lazić, Katarina, Radulovacki, Miodrag, Carley, David W, "Sleep-state related EEG amplitude distribution in the rat model of cortical cholinergic innervation disorder" in Sleep and Biological Rhythms, 11, no. 2 (2013):243-115,
https://hdl.handle.net/21.15107/rcub_ibiss_1027 .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Lazić, Katarina
AU  - Ćirić, Jelena
AU  - Kalauzi, Aleksandar
AU  - Šaponjić, Jasna
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/949
AB  - In order to identify the differences for the onset and progression of functionally distinct cholinergic innervation disorders, we investigated the effect of bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesions on sleep/wake states and electroencephalographic (EEG) microstructure in rats, chronically implanted for sleep recording. Bilateral NB lesion transiently altered Wake/NREM duration within the sensorimotor cortex, and Wake/REM duration within the motor cortex, while there was no change in the sleep/wake states distributions following the bilateral PPT lesion. Bilateral PPT lesion sustainably increased the Wake/REM and REM/Wake transitions followed by inconsistent dysregulation of the NREM/REM and REM/NREM transitions in sensorimotor cortex, but oppositely by their increment throughout four weeks in motor cortex. Bilateral NB lesion sustainably decreased the NREM/REM and REM/NREM transitions during four weeks in the sensorimotor cortex, but oppositely increased them in the motor cortex. We have shown that the sustained beta and gamma augmentation within the sensorimotor and motor cortex, and across all sleep/wake states, simultaneously with Wake delta amplitude attenuation only within the sensorimotor cortex, were the underlying EEG microstructure for the sleep/wake states-transitions structure disturbance following bilateral PPT lesion. In contrast, the bilateral NB lesion only augmented REM theta in sensorimotor cortex during three weeks. We have shown that the NB and PPT lesions induced differing, structure-related EEG microstructure and transition structure disturbances particularly expressed in motor cortex during NREM and REM sleep. We evidenced for the first time the different topographical expression of the functionally distinct cholinergic neuronal innervation impairment in rat. (C) 2013 Elsevier B.V. All rights reserved.
T2  - Behavioural Brain Research
T1  - Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat
IS  - null
VL  - 256
SP  - 41
EP  - 118
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_949
ER  - 

@article{
author = "Petrović, Jelena and Lazić, Katarina and Ćirić, Jelena and Kalauzi, Aleksandar and Šaponjić, Jasna",
year = "2013",
abstract = "In order to identify the differences for the onset and progression of functionally distinct cholinergic innervation disorders, we investigated the effect of bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesions on sleep/wake states and electroencephalographic (EEG) microstructure in rats, chronically implanted for sleep recording. Bilateral NB lesion transiently altered Wake/NREM duration within the sensorimotor cortex, and Wake/REM duration within the motor cortex, while there was no change in the sleep/wake states distributions following the bilateral PPT lesion. Bilateral PPT lesion sustainably increased the Wake/REM and REM/Wake transitions followed by inconsistent dysregulation of the NREM/REM and REM/NREM transitions in sensorimotor cortex, but oppositely by their increment throughout four weeks in motor cortex. Bilateral NB lesion sustainably decreased the NREM/REM and REM/NREM transitions during four weeks in the sensorimotor cortex, but oppositely increased them in the motor cortex. We have shown that the sustained beta and gamma augmentation within the sensorimotor and motor cortex, and across all sleep/wake states, simultaneously with Wake delta amplitude attenuation only within the sensorimotor cortex, were the underlying EEG microstructure for the sleep/wake states-transitions structure disturbance following bilateral PPT lesion. In contrast, the bilateral NB lesion only augmented REM theta in sensorimotor cortex during three weeks. We have shown that the NB and PPT lesions induced differing, structure-related EEG microstructure and transition structure disturbances particularly expressed in motor cortex during NREM and REM sleep. We evidenced for the first time the different topographical expression of the functionally distinct cholinergic neuronal innervation impairment in rat. (C) 2013 Elsevier B.V. All rights reserved.",
journal = "Behavioural Brain Research",
title = "Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat",
number = "null",
volume = "256",
pages = "41-118",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_949"
}

Petrović, J., Lazić, K., Ćirić, J., Kalauzi, A.,& Šaponjić, J.. (2013). Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat. in Behavioural Brain Research, 256(null), 41-118.
https://hdl.handle.net/21.15107/rcub_ibiss_949

Petrović J, Lazić K, Ćirić J, Kalauzi A, Šaponjić J. Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat. in Behavioural Brain Research. 2013;256(null):41-118.
https://hdl.handle.net/21.15107/rcub_ibiss_949 .

Petrović, Jelena, Lazić, Katarina, Ćirić, Jelena, Kalauzi, Aleksandar, Šaponjić, Jasna, "Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat" in Behavioural Brain Research, 256, no. null (2013):41-118,
https://hdl.handle.net/21.15107/rcub_ibiss_949 .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
AU  - Kalauzi, Aleksandar
AU  - Šaponjić, Jasna
PY  - 2013
UR  - http://www.scopus.com/inward/record.url?eid=2-s2.0-84881370170&partnerID=tZOtx3y1
UR  - http://www.sciencedirect.com/science/article/pii/S0014488613000605
UR  - http://www.ncbi.nlm.nih.gov/pubmed/23481548
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3298
AB  - The pedunculopontine tegmental nucleus (PPT) represents a major aggregation of cholinergic neurons in the mammalian brainstem, which is important in the generation and maintenance of REM sleep. We investigated the effects of unilateral and bilateral PPT lesions on sleep and all the conventional sleep-state related EEG frequency bands amplitudes, in an attempt to find the EEG markers for the onset and progression of PPT cholinergic neuronal degeneration. The experiments were performed on 35 adult male Wistar rats, chronically implanted for sleep recording. During the surgical procedure for EEG and EMG electrodes implantation, the unilateral or bilateral PPT lesion was produced under ketamine/diazepam anesthesia, by the stereotaxically guided microinfusion of 100 nl 0.1M ibotenic acid (IBO) into PPT. We applied Fourier analysis to signals acquired throughout 6h of recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We also calculated the group probability density estimates (PDE) of all Wake, NREM and REM conventional EEG frequency amplitudes, and the number of all the transition states using MATLAB 6.5. Our results show that the unilateral or bilateral PPT lesions did not change the sleep/wake architecture, but did change the sleep/wake state transitions structure and the sleep/state related "EEG microstructure". Unilateral or bilateral PPT lesions sustainably increased Wake/REM and REM/Wake transitions from 14 to 35 days after lesions. This was followed by decreased NREM/REM and REM/NREM transitions from 28 days only in the case of the bilateral PPT lesion. The unilateral PPT lesion augmented both Wake theta and REM beta while it also attenuated the relative amplitude of the Wake delta frequency, with a delay of one week. Following a bilateral PPT lesion there was augmentation of the relative amplitude of the Wake, NREM, and REM beta and REM gamma frequency which occurred simultaneously to NREM and Wake delta attenuation. We have shown that the PPT cholinergic neuronal loss sustainably increased the number of the Wake/REM and REM/Wake transitions and augmented sleep-states related cortical activation that was simultaneously expressed by the high frequency amplitude augmentation, as well as Wake and NREM delta frequency attenuation.
T2  - Experimental Neurology
T1  - Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure.
VL  - 247
DO  - 10.1016/j.expneurol.2013.02.007
SP  - 562
EP  - 71
ER  - 

@article{
author = "Petrović, Jelena and Ćirić, Jelena and Lazić, Katarina and Kalauzi, Aleksandar and Šaponjić, Jasna",
year = "2013",
abstract = "The pedunculopontine tegmental nucleus (PPT) represents a major aggregation of cholinergic neurons in the mammalian brainstem, which is important in the generation and maintenance of REM sleep. We investigated the effects of unilateral and bilateral PPT lesions on sleep and all the conventional sleep-state related EEG frequency bands amplitudes, in an attempt to find the EEG markers for the onset and progression of PPT cholinergic neuronal degeneration. The experiments were performed on 35 adult male Wistar rats, chronically implanted for sleep recording. During the surgical procedure for EEG and EMG electrodes implantation, the unilateral or bilateral PPT lesion was produced under ketamine/diazepam anesthesia, by the stereotaxically guided microinfusion of 100 nl 0.1M ibotenic acid (IBO) into PPT. We applied Fourier analysis to signals acquired throughout 6h of recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We also calculated the group probability density estimates (PDE) of all Wake, NREM and REM conventional EEG frequency amplitudes, and the number of all the transition states using MATLAB 6.5. Our results show that the unilateral or bilateral PPT lesions did not change the sleep/wake architecture, but did change the sleep/wake state transitions structure and the sleep/state related "EEG microstructure". Unilateral or bilateral PPT lesions sustainably increased Wake/REM and REM/Wake transitions from 14 to 35 days after lesions. This was followed by decreased NREM/REM and REM/NREM transitions from 28 days only in the case of the bilateral PPT lesion. The unilateral PPT lesion augmented both Wake theta and REM beta while it also attenuated the relative amplitude of the Wake delta frequency, with a delay of one week. Following a bilateral PPT lesion there was augmentation of the relative amplitude of the Wake, NREM, and REM beta and REM gamma frequency which occurred simultaneously to NREM and Wake delta attenuation. We have shown that the PPT cholinergic neuronal loss sustainably increased the number of the Wake/REM and REM/Wake transitions and augmented sleep-states related cortical activation that was simultaneously expressed by the high frequency amplitude augmentation, as well as Wake and NREM delta frequency attenuation.",
journal = "Experimental Neurology",
title = "Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure.",
volume = "247",
doi = "10.1016/j.expneurol.2013.02.007",
pages = "562-71"
}

Petrović, J., Ćirić, J., Lazić, K., Kalauzi, A.,& Šaponjić, J.. (2013). Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure.. in Experimental Neurology, 247, 562-71.
https://doi.org/10.1016/j.expneurol.2013.02.007

Petrović J, Ćirić J, Lazić K, Kalauzi A, Šaponjić J. Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure.. in Experimental Neurology. 2013;247:562-71.
doi:10.1016/j.expneurol.2013.02.007 .

Petrović, Jelena, Ćirić, Jelena, Lazić, Katarina, Kalauzi, Aleksandar, Šaponjić, Jasna, "Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure." in Experimental Neurology, 247 (2013):562-71,
https://doi.org/10.1016/j.expneurol.2013.02.007 . .

TY  - JOUR
AU  - Kalauzi, Aleksandar
AU  - Spasić, Slađana Z.
AU  - Petrović, Jelena
AU  - Ćirić, Jelena
AU  - Šaponjić, Jasna
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1175
AB  - This study was aimed to explore the sleep/wake states related cortico-pontine theta carrier frequency phase shift following a systemically induced chemical axotomy of the monoaminergic afferents within a brain of the freely moving rats. Our experiments were performed in 14 adult, male Sprague Dawley rats, chronically implanted for sleep recording. We recorded sleep during baseline condition, following sham injection (saline i.p. 1 ml/kg), and every week for 5 weeks following injection of the systemic neurotoxins (DSP-4 or PCA; 1 ml/kg, i.p.) for chemical axotomy of the locus coeruleus (LC) and dorsal raphe (DR) axon terminals. After sleep/wake states identification, FFT analysis was performed on 5 s epochs. Theta carrier frequency phase shift (Delta Phi) was calculated for each epoch by averaging theta Fourier component phase shifts, and the Delta Phi values were plotted for each rat in control condition and 28 days following the monoaminergic lesions, as a time for permanently established DR or LC chemical axotomy. Calculated group averages have shown that Delta Phi increased between pons and cortex significantly in all sleep/wake states (Wake, NREM and REM) following the monoaminergic lesions, with respect to controls. Monoaminergic lesions established the pontine leading role in the brain theta oscillations during all sleep/wake states.
T2  - General Physiology and Biophysics
T1  - Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat
IS  - 2
VL  - 31
EP  - 171
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1175
ER  - 

@article{
author = "Kalauzi, Aleksandar and Spasić, Slađana Z. and Petrović, Jelena and Ćirić, Jelena and Šaponjić, Jasna",
year = "2012",
abstract = "This study was aimed to explore the sleep/wake states related cortico-pontine theta carrier frequency phase shift following a systemically induced chemical axotomy of the monoaminergic afferents within a brain of the freely moving rats. Our experiments were performed in 14 adult, male Sprague Dawley rats, chronically implanted for sleep recording. We recorded sleep during baseline condition, following sham injection (saline i.p. 1 ml/kg), and every week for 5 weeks following injection of the systemic neurotoxins (DSP-4 or PCA; 1 ml/kg, i.p.) for chemical axotomy of the locus coeruleus (LC) and dorsal raphe (DR) axon terminals. After sleep/wake states identification, FFT analysis was performed on 5 s epochs. Theta carrier frequency phase shift (Delta Phi) was calculated for each epoch by averaging theta Fourier component phase shifts, and the Delta Phi values were plotted for each rat in control condition and 28 days following the monoaminergic lesions, as a time for permanently established DR or LC chemical axotomy. Calculated group averages have shown that Delta Phi increased between pons and cortex significantly in all sleep/wake states (Wake, NREM and REM) following the monoaminergic lesions, with respect to controls. Monoaminergic lesions established the pontine leading role in the brain theta oscillations during all sleep/wake states.",
journal = "General Physiology and Biophysics",
title = "Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat",
number = "2",
volume = "31",
pages = "171",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1175"
}

Kalauzi, A., Spasić, S. Z., Petrović, J., Ćirić, J.,& Šaponjić, J.. (2012). Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat. in General Physiology and Biophysics, 31(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1175

Kalauzi A, Spasić SZ, Petrović J, Ćirić J, Šaponjić J. Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat. in General Physiology and Biophysics. 2012;31(2):null-171.
https://hdl.handle.net/21.15107/rcub_ibiss_1175 .

Kalauzi, Aleksandar, Spasić, Slađana Z., Petrović, Jelena, Ćirić, Jelena, Šaponjić, Jasna, "Cortico-pontine theta carrier frequency phase shift across sleep/wake states following monoaminergic lesion in rat" in General Physiology and Biophysics, 31, no. 2 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1175 .