TY  - CONF
AU  - Nikolić, Ljiljana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5512
AB  - Communication between neurons and astrocytes and its role in information
processing in the brain has been repeatedly demonstrated over the past two decades. Evidence
for neurons communicating with astroglia is solid, but the signaling pathways leading back
from glial-to-neuronal activity are difficult to study and remain highly controversial. There is
a general agreement that intracellular Ca2+ is a key signaling pathway activated in astrocytes in
response to neuronal signals. However, it is still debated whether and how intracellular Ca2+
contributes to the release of gliotransmitters by astrocytes and to their regulation of synaptic
transmission and neuronal excitability [1, 2]. The main limitation causing these controversies
is the difficulty to activate astrocytes in a reliable and specific manner. To overcome this we
used widespread transgenic expression of light-gated cation channel channelrhodopsin-2
specifically in astrocytes. This optogenetic approach enabled us to control astrocyte activity by
the blue light and to study glia-related properties of neuronal activity regulation. Using slice
preparations we found that selective photoactivation of astrocytes reliably evoked glial Ca2+
responses, increased glutamatergic synaptic transmission in the hippocampus and increased
firing of pyramidal neurons [3]. Neuronal firing was regulated by the Ca2+-dependent glutamate
release from astrocytes and activation of neuronal extra-synaptic NMDA receptors. Optical
activation of astrocytes also increased synaptic transmission through activation of presynaptic
metabotropic glutamate receptors in case of pyramidal neurons and presynaptic NMDA
receptors in case of granule cells of the dentate gyrus [3, 4]. In this model of blue light
stimulated astrocytes, Ca2+ increase and subsequent glutamate release were amplified by
ATP/ADP-mediated autocrine activation of purinergic P2Y1 receptors on astrocytes. Using
optogenetic approach targeting astrocytes we revealed that described autocrine purinergic loop
of astroglia is also permanently active in a mouse model of temporal lobe epilepsy and that it
sustains abnormal synaptic activity [4]. Moreover, blockade of P2Y1 receptor-mediated
signaling in the dentate gyrus astrocytes restored regular glutamatergic synaptic transmission
in epilepsy, just as in the case of photoactivated astrocytes. These findings demonstrate that
optogenetic astrocyte activation is an effective approach to study glia-to-neuron
communication and to understand how it perturbs in disease.
REFERENCES
[1] N. Hamilton, D Attwell., Nat. Rev. Neurosci. 11 (2010), 227 238.
[2] N. Bazargani, Attwell, D., Nat. Neurosci. 19 (2016), 182 189.
[3] W. Shen, Lj. Nikolic et al., Sci. Rep. 7 (2017), 11280. J. Appl. Opt. A 33 (1989), 357 376.
[4] Lj.Nikolic, W. Shen et al., Glia. 66 (2018), 2673-2683.
PB  - Belgrade: Institute of Physics
C3  - Book of abstracts: 16th Photonics Workshop: Conference; 2023 Mar 12-15; Kopaonik, Serbia
T1  - Application of optogenetics for studying neuronal activity via glial photostimulation
SP  - 47
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5512
ER  - 

@conference{
author = "Nikolić, Ljiljana",
year = "2023",
abstract = "Communication between neurons and astrocytes and its role in information
processing in the brain has been repeatedly demonstrated over the past two decades. Evidence
for neurons communicating with astroglia is solid, but the signaling pathways leading back
from glial-to-neuronal activity are difficult to study and remain highly controversial. There is
a general agreement that intracellular Ca2+ is a key signaling pathway activated in astrocytes in
response to neuronal signals. However, it is still debated whether and how intracellular Ca2+
contributes to the release of gliotransmitters by astrocytes and to their regulation of synaptic
transmission and neuronal excitability [1, 2]. The main limitation causing these controversies
is the difficulty to activate astrocytes in a reliable and specific manner. To overcome this we
used widespread transgenic expression of light-gated cation channel channelrhodopsin-2
specifically in astrocytes. This optogenetic approach enabled us to control astrocyte activity by
the blue light and to study glia-related properties of neuronal activity regulation. Using slice
preparations we found that selective photoactivation of astrocytes reliably evoked glial Ca2+
responses, increased glutamatergic synaptic transmission in the hippocampus and increased
firing of pyramidal neurons [3]. Neuronal firing was regulated by the Ca2+-dependent glutamate
release from astrocytes and activation of neuronal extra-synaptic NMDA receptors. Optical
activation of astrocytes also increased synaptic transmission through activation of presynaptic
metabotropic glutamate receptors in case of pyramidal neurons and presynaptic NMDA
receptors in case of granule cells of the dentate gyrus [3, 4]. In this model of blue light
stimulated astrocytes, Ca2+ increase and subsequent glutamate release were amplified by
ATP/ADP-mediated autocrine activation of purinergic P2Y1 receptors on astrocytes. Using
optogenetic approach targeting astrocytes we revealed that described autocrine purinergic loop
of astroglia is also permanently active in a mouse model of temporal lobe epilepsy and that it
sustains abnormal synaptic activity [4]. Moreover, blockade of P2Y1 receptor-mediated
signaling in the dentate gyrus astrocytes restored regular glutamatergic synaptic transmission
in epilepsy, just as in the case of photoactivated astrocytes. These findings demonstrate that
optogenetic astrocyte activation is an effective approach to study glia-to-neuron
communication and to understand how it perturbs in disease.
REFERENCES
[1] N. Hamilton, D Attwell., Nat. Rev. Neurosci. 11 (2010), 227 238.
[2] N. Bazargani, Attwell, D., Nat. Neurosci. 19 (2016), 182 189.
[3] W. Shen, Lj. Nikolic et al., Sci. Rep. 7 (2017), 11280. J. Appl. Opt. A 33 (1989), 357 376.
[4] Lj.Nikolic, W. Shen et al., Glia. 66 (2018), 2673-2683.",
publisher = "Belgrade: Institute of Physics",
journal = "Book of abstracts: 16th Photonics Workshop: Conference; 2023 Mar 12-15; Kopaonik, Serbia",
title = "Application of optogenetics for studying neuronal activity via glial photostimulation",
pages = "47",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5512"
}

Nikolić, L.. (2023). Application of optogenetics for studying neuronal activity via glial photostimulation. in Book of abstracts: 16th Photonics Workshop: Conference; 2023 Mar 12-15; Kopaonik, Serbia
Belgrade: Institute of Physics., 47.
https://hdl.handle.net/21.15107/rcub_ibiss_5512

Nikolić L. Application of optogenetics for studying neuronal activity via glial photostimulation. in Book of abstracts: 16th Photonics Workshop: Conference; 2023 Mar 12-15; Kopaonik, Serbia. 2023;:47.
https://hdl.handle.net/21.15107/rcub_ibiss_5512 .

Nikolić, Ljiljana, "Application of optogenetics for studying neuronal activity via glial photostimulation" in Book of abstracts: 16th Photonics Workshop: Conference; 2023 Mar 12-15; Kopaonik, Serbia (2023):47,
https://hdl.handle.net/21.15107/rcub_ibiss_5512 .

TY  - JOUR
AU  - Milićević, Katarina
AU  - Bataveljić, Danijela
AU  - Bogdanović Pristov, Jelena
AU  - Anđus, Pavle
AU  - Nikolić, Ljiljana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6022
AB  - In multiple sclerosis (MS), glial cells astrocytes interact with the autoreactive immune
cells that attack the central nervous system (CNS), which causes and sustains neuroinflammation.
However, little is known about the direct interaction between these cells when they are in close
proximity in the inflamed CNS. By using an experimental autoimmune encephalomyelitis (EAE)
model of MS, we previously found that in the proximity of autoreactive CNS-infiltrated immune cells
(CNS-IICs), astrocytes respond with a rapid calcium increase that is mediated by the autocrine P2X7
receptor (P2X7R) activation. We now reveal that the mechanisms regulating this direct interaction
of astrocytes and CNS-IICs involve the coupling between P2X7R, connexin-43, and β3-integrin. We
found that P2X7R and astroglial connexin-43 interact and concentrate in the immediate proximity of
the CNS-IICs in EAE. P2X7R also interacts with β3-integrin, and the block of astroglial αvβ3-integrin
reduces the P2X7R-dependent calcium response of astrocytes upon encountering CNS-IICs. This
interaction was dependent on astroglial mitochondrial activity, which regulated the ATP-driven
P2X7R activation and facilitated the termination of the astrocytic calcium response evoked by CNS-
IICs. By further defining the interactions between the CNS and the immune system, our findings
provide a novel perspective toward expanding integrin-targeting therapeutic approaches for MS
treatment by controlling the cell–cell interactions between astrocytes and CNS-IICs.
PB  - MDPI
PB  - Basel: MDPI
T2  - Cells
T1  - Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43
IS  - 13
VL  - 12
DO  - 10.3390/cells12131786
SP  - 1786
ER  - 

@article{
author = "Milićević, Katarina and Bataveljić, Danijela and Bogdanović Pristov, Jelena and Anđus, Pavle and Nikolić, Ljiljana",
year = "2023",
abstract = "In multiple sclerosis (MS), glial cells astrocytes interact with the autoreactive immune
cells that attack the central nervous system (CNS), which causes and sustains neuroinflammation.
However, little is known about the direct interaction between these cells when they are in close
proximity in the inflamed CNS. By using an experimental autoimmune encephalomyelitis (EAE)
model of MS, we previously found that in the proximity of autoreactive CNS-infiltrated immune cells
(CNS-IICs), astrocytes respond with a rapid calcium increase that is mediated by the autocrine P2X7
receptor (P2X7R) activation. We now reveal that the mechanisms regulating this direct interaction
of astrocytes and CNS-IICs involve the coupling between P2X7R, connexin-43, and β3-integrin. We
found that P2X7R and astroglial connexin-43 interact and concentrate in the immediate proximity of
the CNS-IICs in EAE. P2X7R also interacts with β3-integrin, and the block of astroglial αvβ3-integrin
reduces the P2X7R-dependent calcium response of astrocytes upon encountering CNS-IICs. This
interaction was dependent on astroglial mitochondrial activity, which regulated the ATP-driven
P2X7R activation and facilitated the termination of the astrocytic calcium response evoked by CNS-
IICs. By further defining the interactions between the CNS and the immune system, our findings
provide a novel perspective toward expanding integrin-targeting therapeutic approaches for MS
treatment by controlling the cell–cell interactions between astrocytes and CNS-IICs.",
publisher = "MDPI, Basel: MDPI",
journal = "Cells",
title = "Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43",
number = "13",
volume = "12",
doi = "10.3390/cells12131786",
pages = "1786"
}

Milićević, K., Bataveljić, D., Bogdanović Pristov, J., Anđus, P.,& Nikolić, L.. (2023). Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43. in Cells
MDPI., 12(13), 1786.
https://doi.org/10.3390/cells12131786

Milićević K, Bataveljić D, Bogdanović Pristov J, Anđus P, Nikolić L. Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43. in Cells. 2023;12(13):1786.
doi:10.3390/cells12131786 .

Milićević, Katarina, Bataveljić, Danijela, Bogdanović Pristov, Jelena, Anđus, Pavle, Nikolić, Ljiljana, "Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, β3-Integrin, and Connexin-43" in Cells, 12, no. 13 (2023):1786,
https://doi.org/10.3390/cells12131786 . .

TY  - CONF
AU  - Milićević, Katarina
AU  - Bataveljić, Danijela
AU  - Bogdanović Pristov, Jelena
AU  - Anđus, Pavle
AU  - Nikolić, Ljiljana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6021
AB  - Astrocytes form a dense meshwork throughout the central nervous system (CNS) which qualifies them to perform interactive maintenance functions with neighboring cells. In neuroinflammation, this astroglial cell-to-cell interaction varies which can either promote or lessen pathological processes (1,2). In multiple sclerosis (MS), astrocytes engage in an interaction with immune cells which drives neurodegeneration by creating and sustaining an inflammatory CNS environment (3). Previously, we showed that CNS-infiltrated immune cells (CNS-IICs) in the experimental autoimmune encephalomyelitis (EAE) rat, rapidly alter the activity pattern of astrocytes by activating glial P2X7 receptor (P2X7R)(4). In the present study, we aimed to identify the properties of astroglial P2X7R in EAE and to identify mechanisms responsible for astrocyte activation in the presence of CNS-IICs (CD4+ T cells). In this respect, spinal cords from rats at the peak of EAE and age-matched healthy controls were isolated and protein expression of P2X7R and connexin-43 (Cx-43) were investigated. P2X7R protein expression was decreased in the lumbar spinal cord, while Cx-43 did not change. Next, we found that P2X7R and Cx-43 proteins interact in the lumbar spinal cord since both the monomer and the dimer Cx-43 co-immunoprecipitate with P2X7R. Even though the colocalization of P2X7R and Cx-43 was decreased in EAE compared to the control, the analysis of the distribution of astroglial P2X7R and Cx-43 and their colocalization in the radius of 20 μm from the infiltrated CD4+ T cell center showed that astroglial P2X7R and Cx-43 are specifically associated and concentrated in the proximity of CNS-IICs in the EAE spinal cord. Subsequently, to achieve an unambiguous analysis of astrocyte-immune cell interaction, we monitored Ca2+
dynamics in Fluo-4 labeled cultured naïve astrocytes following brief bath-application of CNS-IICs isolated and purified from spinal cords of EAE rats. Our data suggest that astroglial αvβ3-integrin acted upstream of P2X7R activation and is likely involved in establishing initial contact of astrocytes with CNS-IICs since astrocytic αvβ3-integrin block reduced the astrocytic Ca2+ response to CNS-IIC application. Furthermore, astrocytes challenged with CGP31157 (blocker of mNCLX and HCX) exhibited a prolonged intracellular Ca2+ elevation and higher ATP release after brief exposure to CNS-IICs, indicating a regulatory function of mitochondria on this intracellular astrocyte Ca2+ response. Collectively
these data describing integrin-relevant cellular mechanisms of astroglial P2X7R activation could help to expand integrin-inhibiting therapeutic approaches currently in use for MS treatment toward control of astrocyte purine-based interaction with immune cells.
PB  - Hoboken: John Wiley and Sons
C3  - XVI European Meeting on Glial Cells in Health and Disease; 2023 Jul 8-11; Berlin, Germany
T1  - P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells
DO  - 10.1002/glia.24419
SP  - E941
EP  - E942
ER  - 

@conference{
author = "Milićević, Katarina and Bataveljić, Danijela and Bogdanović Pristov, Jelena and Anđus, Pavle and Nikolić, Ljiljana",
year = "2023",
abstract = "Astrocytes form a dense meshwork throughout the central nervous system (CNS) which qualifies them to perform interactive maintenance functions with neighboring cells. In neuroinflammation, this astroglial cell-to-cell interaction varies which can either promote or lessen pathological processes (1,2). In multiple sclerosis (MS), astrocytes engage in an interaction with immune cells which drives neurodegeneration by creating and sustaining an inflammatory CNS environment (3). Previously, we showed that CNS-infiltrated immune cells (CNS-IICs) in the experimental autoimmune encephalomyelitis (EAE) rat, rapidly alter the activity pattern of astrocytes by activating glial P2X7 receptor (P2X7R)(4). In the present study, we aimed to identify the properties of astroglial P2X7R in EAE and to identify mechanisms responsible for astrocyte activation in the presence of CNS-IICs (CD4+ T cells). In this respect, spinal cords from rats at the peak of EAE and age-matched healthy controls were isolated and protein expression of P2X7R and connexin-43 (Cx-43) were investigated. P2X7R protein expression was decreased in the lumbar spinal cord, while Cx-43 did not change. Next, we found that P2X7R and Cx-43 proteins interact in the lumbar spinal cord since both the monomer and the dimer Cx-43 co-immunoprecipitate with P2X7R. Even though the colocalization of P2X7R and Cx-43 was decreased in EAE compared to the control, the analysis of the distribution of astroglial P2X7R and Cx-43 and their colocalization in the radius of 20 μm from the infiltrated CD4+ T cell center showed that astroglial P2X7R and Cx-43 are specifically associated and concentrated in the proximity of CNS-IICs in the EAE spinal cord. Subsequently, to achieve an unambiguous analysis of astrocyte-immune cell interaction, we monitored Ca2+
dynamics in Fluo-4 labeled cultured naïve astrocytes following brief bath-application of CNS-IICs isolated and purified from spinal cords of EAE rats. Our data suggest that astroglial αvβ3-integrin acted upstream of P2X7R activation and is likely involved in establishing initial contact of astrocytes with CNS-IICs since astrocytic αvβ3-integrin block reduced the astrocytic Ca2+ response to CNS-IIC application. Furthermore, astrocytes challenged with CGP31157 (blocker of mNCLX and HCX) exhibited a prolonged intracellular Ca2+ elevation and higher ATP release after brief exposure to CNS-IICs, indicating a regulatory function of mitochondria on this intracellular astrocyte Ca2+ response. Collectively
these data describing integrin-relevant cellular mechanisms of astroglial P2X7R activation could help to expand integrin-inhibiting therapeutic approaches currently in use for MS treatment toward control of astrocyte purine-based interaction with immune cells.",
publisher = "Hoboken: John Wiley and Sons",
journal = "XVI European Meeting on Glial Cells in Health and Disease; 2023 Jul 8-11; Berlin, Germany",
title = "P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells",
doi = "10.1002/glia.24419",
pages = "E941-E942"
}

Milićević, K., Bataveljić, D., Bogdanović Pristov, J., Anđus, P.,& Nikolić, L.. (2023). P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells. in XVI European Meeting on Glial Cells in Health and Disease; 2023 Jul 8-11; Berlin, Germany
Hoboken: John Wiley and Sons., E941-E942.
https://doi.org/10.1002/glia.24419

Milićević K, Bataveljić D, Bogdanović Pristov J, Anđus P, Nikolić L. P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells. in XVI European Meeting on Glial Cells in Health and Disease; 2023 Jul 8-11; Berlin, Germany. 2023;:E941-E942.
doi:10.1002/glia.24419 .

Milićević, Katarina, Bataveljić, Danijela, Bogdanović Pristov, Jelena, Anđus, Pavle, Nikolić, Ljiljana, "P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells" in XVI European Meeting on Glial Cells in Health and Disease; 2023 Jul 8-11; Berlin, Germany (2023):E941-E942,
https://doi.org/10.1002/glia.24419 . .

TY  - JOUR
AU  - Shen, Weida
AU  - Bogdanović Pristov, Jelena
AU  - Nobili, Paola
AU  - Nikolić, Ljiljana
PY  - 2023
UR  - https://journals.lww.com/10.4103/1673-5374.360281
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5383
AB  - Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges. The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons. However, approximately 30% of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70% of patients can be alleviated but not completely removed by the current medications. Thus, new strategies for the treatment of epilepsy are in urgent demand. Over the past decades, with the increase in knowledge on the role of glia in the genesis and development of epilepsy, glial cells are receiving renewed attention. In a normal brain, glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function. In epilepsy, however, the supportive roles of glial cells are compromised, and their interaction with neurons is altered, which disrupts brain function. In this review, we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity, with the major focus on the dysfunction of astroglial potassium channels, water channels, gap junctions, glutamate transporters, purinergic signaling, synaptogenesis, on the roles of microglial inflammatory cytokines, microglia-astrocyte interactions in epilepsy, and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain. These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.
T2  - Neural Regeneration Research
T1  - Can glial cells save neurons in epilepsy?
IS  - 7
VL  - 18
DO  - 10.4103/1673-5374.360281
SP  - 1417
EP  - 1422
ER  - 

@article{
author = "Shen, Weida and Bogdanović Pristov, Jelena and Nobili, Paola and Nikolić, Ljiljana",
year = "2023",
abstract = "Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges. The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons. However, approximately 30% of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70% of patients can be alleviated but not completely removed by the current medications. Thus, new strategies for the treatment of epilepsy are in urgent demand. Over the past decades, with the increase in knowledge on the role of glia in the genesis and development of epilepsy, glial cells are receiving renewed attention. In a normal brain, glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function. In epilepsy, however, the supportive roles of glial cells are compromised, and their interaction with neurons is altered, which disrupts brain function. In this review, we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity, with the major focus on the dysfunction of astroglial potassium channels, water channels, gap junctions, glutamate transporters, purinergic signaling, synaptogenesis, on the roles of microglial inflammatory cytokines, microglia-astrocyte interactions in epilepsy, and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain. These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.",
journal = "Neural Regeneration Research",
title = "Can glial cells save neurons in epilepsy?",
number = "7",
volume = "18",
doi = "10.4103/1673-5374.360281",
pages = "1417-1422"
}

Shen, W., Bogdanović Pristov, J., Nobili, P.,& Nikolić, L.. (2023). Can glial cells save neurons in epilepsy?. in Neural Regeneration Research, 18(7), 1417-1422.
https://doi.org/10.4103/1673-5374.360281

Shen W, Bogdanović Pristov J, Nobili P, Nikolić L. Can glial cells save neurons in epilepsy?. in Neural Regeneration Research. 2023;18(7):1417-1422.
doi:10.4103/1673-5374.360281 .

Shen, Weida, Bogdanović Pristov, Jelena, Nobili, Paola, Nikolić, Ljiljana, "Can glial cells save neurons in epilepsy?" in Neural Regeneration Research, 18, no. 7 (2023):1417-1422,
https://doi.org/10.4103/1673-5374.360281 . .

TY  - CONF
AU  - Nikolić, Ljiljana
AU  - Bataveljić, Danijela
AU  - Bijelić, Dunja
AU  - Milićević, Katarina
AU  - Bogdanović Pristov, Jelena
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5835
AB  - The neurotransmitter norepinephrine (NE) plays a central role in regulating arousal,
attention, cognitive function and stress responses. Unlike fast neurotransmitters which
act at synapses, NE is released in the neuropil and performs multiple targeting in the
surrounding area. The glial cells astrocytes are a direct target of NE, as they express
all adrenergic receptor subtypes and respond with Ca2+ increases to NE. Astroglial
responses elicited by strong and transient increases of NE in the brain are well studied,
but the effect of a low background NE concentration on astrocytes is unknown. This
background level of NE is maintained by basal noradrenergic activity and is
constantly present in the brain. Therefore, the response of astrocytes to the
background NE could have been unintentionally evoked in previous studies but its
effect overlooked.

To assess action of background NE on astrocytes we combined the whole-cell patch-
clamp, immunohistochemistry, Ca2+ imaging and pharmacology. We used cultured

cortical astrocytes to bypass NE targeting of multiple cell types.
We show that cortical astrocytes detect and respond to the background NE
concentration with an increase in intracellular Ca2+. This Ca2+ liberated from
intracellular stores further increased large-conductance, Ca2+-sensitive potassium
(BK) currents in astrocytes. Notably, immunohistochemistry data showed that BK
channels and alpha 1 adrenoreceptor are highly expressed in astrocytes in the rat
cortex. Furthermore, stimulation of astrocytes by background NE was inhibited by
alpha-adrenoceptor antagonist.
Our results suggest that astrocytes maintain basal brain activity by perceiving and
responding to the background NE.
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  - Background norepinephrine impacts activity of cortical astrocytes
SP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5835
ER  - 

@conference{
author = "Nikolić, Ljiljana and Bataveljić, Danijela and Bijelić, Dunja and Milićević, Katarina and Bogdanović Pristov, Jelena",
year = "2023",
abstract = "The neurotransmitter norepinephrine (NE) plays a central role in regulating arousal,
attention, cognitive function and stress responses. Unlike fast neurotransmitters which
act at synapses, NE is released in the neuropil and performs multiple targeting in the
surrounding area. The glial cells astrocytes are a direct target of NE, as they express
all adrenergic receptor subtypes and respond with Ca2+ increases to NE. Astroglial
responses elicited by strong and transient increases of NE in the brain are well studied,
but the effect of a low background NE concentration on astrocytes is unknown. This
background level of NE is maintained by basal noradrenergic activity and is
constantly present in the brain. Therefore, the response of astrocytes to the
background NE could have been unintentionally evoked in previous studies but its
effect overlooked.

To assess action of background NE on astrocytes we combined the whole-cell patch-
clamp, immunohistochemistry, Ca2+ imaging and pharmacology. We used cultured

cortical astrocytes to bypass NE targeting of multiple cell types.
We show that cortical astrocytes detect and respond to the background NE
concentration with an increase in intracellular Ca2+. This Ca2+ liberated from
intracellular stores further increased large-conductance, Ca2+-sensitive potassium
(BK) currents in astrocytes. Notably, immunohistochemistry data showed that BK
channels and alpha 1 adrenoreceptor are highly expressed in astrocytes in the rat
cortex. Furthermore, stimulation of astrocytes by background NE was inhibited by
alpha-adrenoceptor antagonist.
Our results suggest that astrocytes maintain basal brain activity by perceiving and
responding to the background NE.",
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 = "Background norepinephrine impacts activity of cortical astrocytes",
pages = "51",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5835"
}

Nikolić, L., Bataveljić, D., Bijelić, D., Milićević, K.,& Bogdanović Pristov, J.. (2023). Background norepinephrine impacts activity of cortical astrocytes. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 51.
https://hdl.handle.net/21.15107/rcub_ibiss_5835

Nikolić L, Bataveljić D, Bijelić D, Milićević K, Bogdanović Pristov J. Background norepinephrine impacts activity of cortical astrocytes. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:51.
https://hdl.handle.net/21.15107/rcub_ibiss_5835 .

Nikolić, Ljiljana, Bataveljić, Danijela, Bijelić, Dunja, Milićević, Katarina, Bogdanović Pristov, Jelena, "Background norepinephrine impacts activity of cortical astrocytes" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):51,
https://hdl.handle.net/21.15107/rcub_ibiss_5835 .

TY  - CONF
AU  - Milićević, Katarina
AU  - Bataveljić, Danijela
AU  - Bogdanović Pristov, Jelena
AU  - Anđus, Pavle
AU  - Nikolić, Ljiljana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5837
AB  - The astrocytic network maintains homeostasis in the central nervous system (CNS)
through interactions with neighboring cells. In the CNS autoimmune disease, multiple
sclerosis (MS), neuroinflammatory conditions modulate these cell-to-cell interactions.
Our previous work revealed that the immune cells infiltrated into the CNS (CNS-IICs)
of experimental autoimmune encemphalomyelitis (EAE) rat, an animal model of MS,
rapidly alter the activity pattern of astrocytes by activating the glial P2X7 receptor
(P2X7R). In the present study we further defined the mechanisms responsible for
astrocytes’ activation in the presence of CNS-IICs. For this purpose, we used an in
vitro experimental setup and monitored Ca2+ dynamics in Fluo-4-labeled cultured
naïve astrocytes following brief bath application of CNS-IICs isolated from the spinal
cord of the EAE rat. Our data indicate that the astroglial αvβ3-integrin is involved in
the initial contact of astrocytes with CNS-IICs, since blocking αvβ3-integrin reduced
the expected astrocytic Ca2+ response. Furthermore, blocking of mitochondrial
Na+
/Ca2+- and H+

/Ca2+- exchangers in astrocytes promoted an augmentation of the
intracellular Ca2+ increase and a higher ATP release after brief exposure to CNS-IICs,
demonstrating that mitochondria regulate the astrocyte-CNS IICs cell-cell interaction.
Overall, our study expands the understanding of astrocytes’ interaction with
autoreactive immune cells that are present in their local environment in an
autoimmune disease. This offers a new conceptual framework for considering direct
astrocyte–immune cell interaction to design new strategies for therapy development in
the treatment of MS.
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  - αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells
SP  - 101
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5837
ER  - 

@conference{
author = "Milićević, Katarina and Bataveljić, Danijela and Bogdanović Pristov, Jelena and Anđus, Pavle and Nikolić, Ljiljana",
year = "2023",
abstract = "The astrocytic network maintains homeostasis in the central nervous system (CNS)
through interactions with neighboring cells. In the CNS autoimmune disease, multiple
sclerosis (MS), neuroinflammatory conditions modulate these cell-to-cell interactions.
Our previous work revealed that the immune cells infiltrated into the CNS (CNS-IICs)
of experimental autoimmune encemphalomyelitis (EAE) rat, an animal model of MS,
rapidly alter the activity pattern of astrocytes by activating the glial P2X7 receptor
(P2X7R). In the present study we further defined the mechanisms responsible for
astrocytes’ activation in the presence of CNS-IICs. For this purpose, we used an in
vitro experimental setup and monitored Ca2+ dynamics in Fluo-4-labeled cultured
naïve astrocytes following brief bath application of CNS-IICs isolated from the spinal
cord of the EAE rat. Our data indicate that the astroglial αvβ3-integrin is involved in
the initial contact of astrocytes with CNS-IICs, since blocking αvβ3-integrin reduced
the expected astrocytic Ca2+ response. Furthermore, blocking of mitochondrial
Na+
/Ca2+- and H+

/Ca2+- exchangers in astrocytes promoted an augmentation of the
intracellular Ca2+ increase and a higher ATP release after brief exposure to CNS-IICs,
demonstrating that mitochondria regulate the astrocyte-CNS IICs cell-cell interaction.
Overall, our study expands the understanding of astrocytes’ interaction with
autoreactive immune cells that are present in their local environment in an
autoimmune disease. This offers a new conceptual framework for considering direct
astrocyte–immune cell interaction to design new strategies for therapy development in
the treatment of MS.",
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 = "αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells",
pages = "101",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5837"
}

Milićević, K., Bataveljić, D., Bogdanović Pristov, J., Anđus, P.,& Nikolić, L.. (2023). αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 101.
https://hdl.handle.net/21.15107/rcub_ibiss_5837

Milićević K, Bataveljić D, Bogdanović Pristov J, Anđus P, Nikolić L. αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:101.
https://hdl.handle.net/21.15107/rcub_ibiss_5837 .

Milićević, Katarina, Bataveljić, Danijela, Bogdanović Pristov, Jelena, Anđus, Pavle, Nikolić, Ljiljana, "αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):101,
https://hdl.handle.net/21.15107/rcub_ibiss_5837 .

TY  - CONF
AU  - Milošević, Ana
AU  - Milošević, Katarina
AU  - Nikolić, Ljiljana
AU  - Bogdanović Pristov, Jelena
AU  - Božić, Iva
AU  - Živković, Anica
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5836
AB  - Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that controls
mammalian reproduction by acting on its receptor (GnRHR) expressed on pituitary
gonadotrope cells. While GnRHR signaling in gonadotropes is well described,
knowledge of GnRHR activation-related events at extrapituitary sites including
neurons is limited. It was proposed that GnRH analogs (GnRHa) induce distinct
changes in hippocampal gene expression, emotional processes, and cognitive
functions.
To explore neuronal GnRHR signaling we used the human neuroblastoma cell line
SH-SY5Y. Further, we explored the regional expression of Gnrhr in rat brain and
investigated the expression of several relevant genes in the hippocampus and preoptic
area of peripubertal male rats treated with GnRHa.
GNRHR is expressed in SH-SY5Y cell line, but its expression does not change after
adding GnRHa in the incubation media. Electrophysiological recordings confirmed
that GnRHa induced membrane depolarization but could not evoke action potentials.
In the rat brain, Gnrhr expression could be detected in the hippocampus, amygdala,
and hypothalamus, including the preoptic area. Prolonged treatment of peripubertal
rats with GnRHa had no effect on the expression of genes in the hippocampus
previously shown to be affected in the sheep model of delayed puberty.
These results imply that neuronal GnRHR is either differently coupled (not coupled
with Gq/11 protein), or that its membrane density is too low to induce transcriptional
events. More investigation is needed to elucidate the role(s) of GnRH-GnRHR
signaling in the brain.
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  - GnRHR signaling in neuronal cells: in vitro and in vivo data
SP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5836
ER  - 

@conference{
author = "Milošević, Ana and Milošević, Katarina and Nikolić, Ljiljana and Bogdanović Pristov, Jelena and Božić, Iva and Živković, Anica and Lavrnja, Irena and Savić, Danijela and Janjić, Marija and Bjelobaba, Ivana",
year = "2023",
abstract = "Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that controls
mammalian reproduction by acting on its receptor (GnRHR) expressed on pituitary
gonadotrope cells. While GnRHR signaling in gonadotropes is well described,
knowledge of GnRHR activation-related events at extrapituitary sites including
neurons is limited. It was proposed that GnRH analogs (GnRHa) induce distinct
changes in hippocampal gene expression, emotional processes, and cognitive
functions.
To explore neuronal GnRHR signaling we used the human neuroblastoma cell line
SH-SY5Y. Further, we explored the regional expression of Gnrhr in rat brain and
investigated the expression of several relevant genes in the hippocampus and preoptic
area of peripubertal male rats treated with GnRHa.
GNRHR is expressed in SH-SY5Y cell line, but its expression does not change after
adding GnRHa in the incubation media. Electrophysiological recordings confirmed
that GnRHa induced membrane depolarization but could not evoke action potentials.
In the rat brain, Gnrhr expression could be detected in the hippocampus, amygdala,
and hypothalamus, including the preoptic area. Prolonged treatment of peripubertal
rats with GnRHa had no effect on the expression of genes in the hippocampus
previously shown to be affected in the sheep model of delayed puberty.
These results imply that neuronal GnRHR is either differently coupled (not coupled
with Gq/11 protein), or that its membrane density is too low to induce transcriptional
events. More investigation is needed to elucidate the role(s) of GnRH-GnRHR
signaling in the brain.",
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 = "GnRHR signaling in neuronal cells: in vitro and in vivo data",
pages = "53",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5836"
}

Milošević, A., Milošević, K., Nikolić, L., Bogdanović Pristov, J., Božić, I., Živković, A., Lavrnja, I., Savić, D., Janjić, M.,& Bjelobaba, I.. (2023). GnRHR signaling in neuronal cells: in vitro and in vivo data. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 53.
https://hdl.handle.net/21.15107/rcub_ibiss_5836

Milošević A, Milošević K, Nikolić L, Bogdanović Pristov J, Božić I, Živković A, Lavrnja I, Savić D, Janjić M, Bjelobaba I. GnRHR signaling in neuronal cells: in vitro and in vivo data. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:53.
https://hdl.handle.net/21.15107/rcub_ibiss_5836 .

Milošević, Ana, Milošević, Katarina, Nikolić, Ljiljana, Bogdanović Pristov, Jelena, Božić, Iva, Živković, Anica, Lavrnja, Irena, Savić, Danijela, Janjić, Marija, Bjelobaba, Ivana, "GnRHR signaling in neuronal cells: in vitro and in vivo data" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):53,
https://hdl.handle.net/21.15107/rcub_ibiss_5836 .

TY  - CONF
AU  - Anđus, Pavle
AU  - Perić, Mina
AU  - Nikolić, Ljiljana
AU  - Bataveljić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5513
AB  - Non-neuronal cells of glial origin play an essential
role in ALS onset and progression. Amer gaining
knowledge on the role of astrocytes in the disease
with particular reference to the inwardly rectifying
potassium channel Kir4.1 we aimed to examine the
functional properties of microglia and oligodendrocytes in the spinal cord of the ALS SOD1G93A rat
focusing on the expression and functional signilcance of Kir4.1.
Microglia in the ALS rat spinal cords showed
remarkable clustering in ventral horns, already in
presymptomatic animals. Colocalization of Kir4.1
and microglial Iba1 staining was 2-3 times more
abundant in presymptomatic as well as in symptomatic animals compared to individual cells. It was
also shown that these clusters bare a higher accumulation and colocalization of Kir4.1 and Iba1 with
mutated SOD1 compared to individual cells.
se spinal cord microglial cells were cultured and
patch-clamped using an innovative movable microscope stage to facilitate the gigaseal formation.
sese measurements demonstrated a decrease of
Ba2+-sensitive Kir currents.
se expression of Kir4.1 was markedly diminished in the dysmorphic ALS oligodendrocytes of
the degenerative phenotype. se cells isolated and
cultured from the SOD1G93A spinal cord showed
no change in processes ramilcation, but expressed
a lower level of Kir4.1. Whole-cell patch-clamp
recordings revealed compromised membrane
biophysical properties and diminished inward currents in ALS oligodendrocytes, with a particularly
decreased Ba2+-sensitive Kir current.
Altogether, our lndings provide the evidence
of a modiled Kir4.1 expression and function in
SOD1G93A glia with this channel’s particular abundance in clusters resembling ALS-specilc plaques.
PB  - Zagreb: Department of Neurology, University Hospital Centre Zagreb
C3  - Abstracts: International Conference on Neurological Disorders and Neurorestoration; 2022 May 19-22; Dubrovnik, Croatia
T1  - Kir4.1 channel- A universal target in ALS glia
SP  - 13
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5513
ER  - 

@conference{
editor = "Mitrečić, Dinko, Petravić, Damir",
author = "Anđus, Pavle and Perić, Mina and Nikolić, Ljiljana and Bataveljić, Danijela",
year = "2022",
abstract = "Non-neuronal cells of glial origin play an essential
role in ALS onset and progression. Amer gaining
knowledge on the role of astrocytes in the disease
with particular reference to the inwardly rectifying
potassium channel Kir4.1 we aimed to examine the
functional properties of microglia and oligodendrocytes in the spinal cord of the ALS SOD1G93A rat
focusing on the expression and functional signilcance of Kir4.1.
Microglia in the ALS rat spinal cords showed
remarkable clustering in ventral horns, already in
presymptomatic animals. Colocalization of Kir4.1
and microglial Iba1 staining was 2-3 times more
abundant in presymptomatic as well as in symptomatic animals compared to individual cells. It was
also shown that these clusters bare a higher accumulation and colocalization of Kir4.1 and Iba1 with
mutated SOD1 compared to individual cells.
se spinal cord microglial cells were cultured and
patch-clamped using an innovative movable microscope stage to facilitate the gigaseal formation.
sese measurements demonstrated a decrease of
Ba2+-sensitive Kir currents.
se expression of Kir4.1 was markedly diminished in the dysmorphic ALS oligodendrocytes of
the degenerative phenotype. se cells isolated and
cultured from the SOD1G93A spinal cord showed
no change in processes ramilcation, but expressed
a lower level of Kir4.1. Whole-cell patch-clamp
recordings revealed compromised membrane
biophysical properties and diminished inward currents in ALS oligodendrocytes, with a particularly
decreased Ba2+-sensitive Kir current.
Altogether, our lndings provide the evidence
of a modiled Kir4.1 expression and function in
SOD1G93A glia with this channel’s particular abundance in clusters resembling ALS-specilc plaques.",
publisher = "Zagreb: Department of Neurology, University Hospital Centre Zagreb",
journal = "Abstracts: International Conference on Neurological Disorders and Neurorestoration; 2022 May 19-22; Dubrovnik, Croatia",
title = "Kir4.1 channel- A universal target in ALS glia",
pages = "13",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5513"
}

Mitrečić, D., Petravić, D., Anđus, P., Perić, M., Nikolić, L.,& Bataveljić, D.. (2022). Kir4.1 channel- A universal target in ALS glia. in Abstracts: International Conference on Neurological Disorders and Neurorestoration; 2022 May 19-22; Dubrovnik, Croatia
Zagreb: Department of Neurology, University Hospital Centre Zagreb., 13.
https://hdl.handle.net/21.15107/rcub_ibiss_5513

Mitrečić D, Petravić D, Anđus P, Perić M, Nikolić L, Bataveljić D. Kir4.1 channel- A universal target in ALS glia. in Abstracts: International Conference on Neurological Disorders and Neurorestoration; 2022 May 19-22; Dubrovnik, Croatia. 2022;:13.
https://hdl.handle.net/21.15107/rcub_ibiss_5513 .

Mitrečić, Dinko, Petravić, Damir, Anđus, Pavle, Perić, Mina, Nikolić, Ljiljana, Bataveljić, Danijela, "Kir4.1 channel- A universal target in ALS glia" in Abstracts: International Conference on Neurological Disorders and Neurorestoration; 2022 May 19-22; Dubrovnik, Croatia (2022):13,
https://hdl.handle.net/21.15107/rcub_ibiss_5513 .

TY  - JOUR
AU  - Nobili, Paola
AU  - Shen, Weida
AU  - Milićević, Katarina
AU  - Bogdanović Pristov, Jelena
AU  - Audinat, Etienne
AU  - Nikolić, Ljiljana
PY  - 2022
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2022.900337/full
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4989
AB  - Epilepsy and multiple sclerosis (MS), two of the most common neurological diseases, are characterized by the establishment of inflammatory environment in the central nervous system that drives disease progression and impacts on neurodegeneration. Current therapeutic approaches in the treatments of epilepsy and MS are targeting neuronal activity and immune cell response, respectively. However, the lack of fully efficient responses to the available treatments obviously shows the need to search for novel therapeutic candidates that will not exclusively target neurons or immune cells. Accumulating knowledge on epilepsy and MS in humans and analysis of relevant animal models, reveals that astrocytes are promising therapeutic candidates to target as they participate in the modulation of the neuroinflammatory response in both diseases from the initial stages and may play an important role in their development. Indeed, astrocytes respond to reactive immune cells and contribute to the neuronal hyperactivity in the inflamed brain. Mechanistically, these astrocytic cell to cell interactions are fundamentally mediated by the purinergic signalling and involve metabotropic P2Y1 receptors in case of astrocyte interactions with neurons, while ionotropic P2X7 receptors are mainly involved in astrocyte interactions with autoreactive immune cells. Herein, we review the potential of targeting astrocytic purinergic signalling mediated by P2Y1 and P2X7 receptors to develop novel approaches for treatments of epilepsy and MS at very early stages.
PB  - Lausanne: Frontiers Media S.A.
T2  - Frontiers in Pharmacology
T1  - Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.
VL  - 13
DO  - 10.3389/fphar.2022.900337
SP  - 900337
ER  - 

@article{
author = "Nobili, Paola and Shen, Weida and Milićević, Katarina and Bogdanović Pristov, Jelena and Audinat, Etienne and Nikolić, Ljiljana",
year = "2022",
abstract = "Epilepsy and multiple sclerosis (MS), two of the most common neurological diseases, are characterized by the establishment of inflammatory environment in the central nervous system that drives disease progression and impacts on neurodegeneration. Current therapeutic approaches in the treatments of epilepsy and MS are targeting neuronal activity and immune cell response, respectively. However, the lack of fully efficient responses to the available treatments obviously shows the need to search for novel therapeutic candidates that will not exclusively target neurons or immune cells. Accumulating knowledge on epilepsy and MS in humans and analysis of relevant animal models, reveals that astrocytes are promising therapeutic candidates to target as they participate in the modulation of the neuroinflammatory response in both diseases from the initial stages and may play an important role in their development. Indeed, astrocytes respond to reactive immune cells and contribute to the neuronal hyperactivity in the inflamed brain. Mechanistically, these astrocytic cell to cell interactions are fundamentally mediated by the purinergic signalling and involve metabotropic P2Y1 receptors in case of astrocyte interactions with neurons, while ionotropic P2X7 receptors are mainly involved in astrocyte interactions with autoreactive immune cells. Herein, we review the potential of targeting astrocytic purinergic signalling mediated by P2Y1 and P2X7 receptors to develop novel approaches for treatments of epilepsy and MS at very early stages.",
publisher = "Lausanne: Frontiers Media S.A.",
journal = "Frontiers in Pharmacology",
title = "Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.",
volume = "13",
doi = "10.3389/fphar.2022.900337",
pages = "900337"
}

Nobili, P., Shen, W., Milićević, K., Bogdanović Pristov, J., Audinat, E.,& Nikolić, L.. (2022). Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.. in Frontiers in Pharmacology
Lausanne: Frontiers Media S.A.., 13, 900337.
https://doi.org/10.3389/fphar.2022.900337

Nobili P, Shen W, Milićević K, Bogdanović Pristov J, Audinat E, Nikolić L. Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.. in Frontiers in Pharmacology. 2022;13:900337.
doi:10.3389/fphar.2022.900337 .

Nobili, Paola, Shen, Weida, Milićević, Katarina, Bogdanović Pristov, Jelena, Audinat, Etienne, Nikolić, Ljiljana, "Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis." in Frontiers in Pharmacology, 13 (2022):900337,
https://doi.org/10.3389/fphar.2022.900337 . .

TY  - JOUR
AU  - Perić, Mina
AU  - Bataveljić, Danijela
AU  - Bijelić, Dunja
AU  - Milićević, Katarina
AU  - Andjus, Pavle R.
AU  - Bogdanović Pristov, Jelena
AU  - Nikolić, Ljiljana
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/jemt.24066
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35088507
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4790
AB  - We describe an approach for studying the physiology of single live cells using the conceptionally novel upright microscope/patch-clamp configuration. Electrophysiology experiments typically require a microscope with the fixed stage position and the motion control of the microscope objective. Here, we demonstrate that a microscope with a z-axis movable stage and a fixed objective can also be efficiently used in combination with the patch-clamp technique. We define a set of underlying principles governing the operation of this microscope/patch-clamp configuration and demonstrate its performance in practice using cultured astrocytes, microglia, and oligodendrocytes. Experimental results show that our custom configuration provides stable recordings, has a high success rate of the whole-cell patch-clamp trials, can be effectively applied to study cellular physiology of glial cells, and provides comparable performance and usability to the commercially available systems. Our system can be easily replicated or adapted to suit the needs of the research groups and can be cost-effective in reducing the investments in purchasing additional equipment. We provide step-by-step instructions on implementing an upright microscope with z-axis movable stage as a routine workhorse for patch-clamping.
PB  - Hoboken: John Wiley and Sons Inc.
T2  - Microscopy Research and Technique
T1  - Approach for patch-clamping using an upright microscope with z-axis movable stage.
IS  - 6
VL  - 85
DO  - 10.1002/jemt.24066
SP  - 2095
EP  - 2104
ER  - 

@article{
author = "Perić, Mina and Bataveljić, Danijela and Bijelić, Dunja and Milićević, Katarina and Andjus, Pavle R. and Bogdanović Pristov, Jelena and Nikolić, Ljiljana",
year = "2022",
abstract = "We describe an approach for studying the physiology of single live cells using the conceptionally novel upright microscope/patch-clamp configuration. Electrophysiology experiments typically require a microscope with the fixed stage position and the motion control of the microscope objective. Here, we demonstrate that a microscope with a z-axis movable stage and a fixed objective can also be efficiently used in combination with the patch-clamp technique. We define a set of underlying principles governing the operation of this microscope/patch-clamp configuration and demonstrate its performance in practice using cultured astrocytes, microglia, and oligodendrocytes. Experimental results show that our custom configuration provides stable recordings, has a high success rate of the whole-cell patch-clamp trials, can be effectively applied to study cellular physiology of glial cells, and provides comparable performance and usability to the commercially available systems. Our system can be easily replicated or adapted to suit the needs of the research groups and can be cost-effective in reducing the investments in purchasing additional equipment. We provide step-by-step instructions on implementing an upright microscope with z-axis movable stage as a routine workhorse for patch-clamping.",
publisher = "Hoboken: John Wiley and Sons Inc.",
journal = "Microscopy Research and Technique",
title = "Approach for patch-clamping using an upright microscope with z-axis movable stage.",
number = "6",
volume = "85",
doi = "10.1002/jemt.24066",
pages = "2095-2104"
}

Perić, M., Bataveljić, D., Bijelić, D., Milićević, K., Andjus, P. R., Bogdanović Pristov, J.,& Nikolić, L.. (2022). Approach for patch-clamping using an upright microscope with z-axis movable stage.. in Microscopy Research and Technique
Hoboken: John Wiley and Sons Inc.., 85(6), 2095-2104.
https://doi.org/10.1002/jemt.24066

Perić M, Bataveljić D, Bijelić D, Milićević K, Andjus PR, Bogdanović Pristov J, Nikolić L. Approach for patch-clamping using an upright microscope with z-axis movable stage.. in Microscopy Research and Technique. 2022;85(6):2095-2104.
doi:10.1002/jemt.24066 .

Perić, Mina, Bataveljić, Danijela, Bijelić, Dunja, Milićević, Katarina, Andjus, Pavle R., Bogdanović Pristov, Jelena, Nikolić, Ljiljana, "Approach for patch-clamping using an upright microscope with z-axis movable stage." in Microscopy Research and Technique, 85, no. 6 (2022):2095-2104,
https://doi.org/10.1002/jemt.24066 . .

TY  - CONF
AU  - Milićević, Katarina
AU  - Lazarević, Milica
AU  - Momčilović, Miljana
AU  - Todorović, Nataša
AU  - Petković, Branka
AU  - Stojadinović, Gordana
AU  - Nikolić, Ljiljana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5504
AB  - Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS)
characterized by infiltration of lymphocytes that leads to myelin damage and neurodegeneration.
The complex interaction between CNS-infiltrating immune cells (CNS-IIC) and astrocytes is an
important contributor to the disease progression. Here, we investigate how naïve astrocytes respond
to autoreactive immune cells present in the CNS at different stages of the disease. For this purpose,
CNS-IICs were isolated from the spinal cords of rats with experimental autoimmune
encephalomyelitis at onset, late-onset and the peak of the disease. Naïve astrocytes, isolated from
the spinal cords of wild-type rat pups, responded to brief bath application of CNS-IIC by robust
elevation of intracellular Ca2+ independently of the disease stage. Our data suggest that direct
contact between astrocytes and CNS-IICs induces Ca2+ changes in astrocytes and points to the new
aspect of cell-cell interactions in the propagation of neuroinflammatory response in CNS
autoimmunity.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
T1  - Naïve astrocytes react to CNS-infiltrated immune cells
SP  - 267
EP  - 270
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5504
ER  - 

@conference{
editor = "Čupić, Željko, Anić, Slobodan",
author = "Milićević, Katarina and Lazarević, Milica and Momčilović, Miljana and Todorović, Nataša and Petković, Branka and Stojadinović, Gordana and Nikolić, Ljiljana",
year = "2022",
abstract = "Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system (CNS)
characterized by infiltration of lymphocytes that leads to myelin damage and neurodegeneration.
The complex interaction between CNS-infiltrating immune cells (CNS-IIC) and astrocytes is an
important contributor to the disease progression. Here, we investigate how naïve astrocytes respond
to autoreactive immune cells present in the CNS at different stages of the disease. For this purpose,
CNS-IICs were isolated from the spinal cords of rats with experimental autoimmune
encephalomyelitis at onset, late-onset and the peak of the disease. Naïve astrocytes, isolated from
the spinal cords of wild-type rat pups, responded to brief bath application of CNS-IIC by robust
elevation of intracellular Ca2+ independently of the disease stage. Our data suggest that direct
contact between astrocytes and CNS-IICs induces Ca2+ changes in astrocytes and points to the new
aspect of cell-cell interactions in the propagation of neuroinflammatory response in CNS
autoimmunity.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia",
title = "Naïve astrocytes react to CNS-infiltrated immune cells",
pages = "267-270",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5504"
}

Čupić, Ž., Anić, S., Milićević, K., Lazarević, M., Momčilović, M., Todorović, N., Petković, B., Stojadinović, G.,& Nikolić, L.. (2022). Naïve astrocytes react to CNS-infiltrated immune cells. in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 267-270.
https://hdl.handle.net/21.15107/rcub_ibiss_5504

Čupić Ž, Anić S, Milićević K, Lazarević M, Momčilović M, Todorović N, Petković B, Stojadinović G, Nikolić L. Naïve astrocytes react to CNS-infiltrated immune cells. in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia. 2022;:267-270.
https://hdl.handle.net/21.15107/rcub_ibiss_5504 .

Čupić, Željko, Anić, Slobodan, Milićević, Katarina, Lazarević, Milica, Momčilović, Miljana, Todorović, Nataša, Petković, Branka, Stojadinović, Gordana, Nikolić, Ljiljana, "Naïve astrocytes react to CNS-infiltrated immune cells" in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia (2022):267-270,
https://hdl.handle.net/21.15107/rcub_ibiss_5504 .

TY  - CONF
AU  - Nikolić, Ljiljana
AU  - Vidović, Marija
AU  - Todorović, Nataša
AU  - Petković, Branka
AU  - Stojadinović, Gordana
AU  - Martać, Ljiljana
AU  - Bogdanović Pristov, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5508
AB  - Investigating membrane properties of plants is a challenging task, considering that success of
experiments is highly dependent on the possibility to isolate metabolically active protoplasts that
can withstand membrane current recordings. The aim of the present work is to obtain viable
protoplasts derived from root cells of Pisum sativum that can be used for the whole-cell patchclamp. We designed the procedure of the pea protoplasts isolation that delivers stable protoplasts
with preserved membrane integrity suitable for electrophysiological experiments. We applied a
custom approach for patch-clamping protoplasts using a microscope with a movable microscope
stage. We recorded prominent inward and prominent outward types of membrane current profiles of
protoplasts. Obtained data indicate that optimized isolation protocol and custom system for patchclamping, can be applied to study membrane properties of root protoplasts.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
T1  - Protoplast patch-clamping using an upright microscope with a movable stage
SP  - 271
EP  - 274
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5508
ER  - 

@conference{
editor = "Čupić, Željko, Anić, Slobodan",
author = "Nikolić, Ljiljana and Vidović, Marija and Todorović, Nataša and Petković, Branka and Stojadinović, Gordana and Martać, Ljiljana and Bogdanović Pristov, Jelena",
year = "2022",
abstract = "Investigating membrane properties of plants is a challenging task, considering that success of
experiments is highly dependent on the possibility to isolate metabolically active protoplasts that
can withstand membrane current recordings. The aim of the present work is to obtain viable
protoplasts derived from root cells of Pisum sativum that can be used for the whole-cell patchclamp. We designed the procedure of the pea protoplasts isolation that delivers stable protoplasts
with preserved membrane integrity suitable for electrophysiological experiments. We applied a
custom approach for patch-clamping protoplasts using a microscope with a movable microscope
stage. We recorded prominent inward and prominent outward types of membrane current profiles of
protoplasts. Obtained data indicate that optimized isolation protocol and custom system for patchclamping, can be applied to study membrane properties of root protoplasts.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia",
title = "Protoplast patch-clamping using an upright microscope with a movable stage",
pages = "271-274",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5508"
}

Čupić, Ž., Anić, S., Nikolić, L., Vidović, M., Todorović, N., Petković, B., Stojadinović, G., Martać, L.,& Bogdanović Pristov, J.. (2022). Protoplast patch-clamping using an upright microscope with a movable stage. in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 271-274.
https://hdl.handle.net/21.15107/rcub_ibiss_5508

Čupić Ž, Anić S, Nikolić L, Vidović M, Todorović N, Petković B, Stojadinović G, Martać L, Bogdanović Pristov J. Protoplast patch-clamping using an upright microscope with a movable stage. in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia. 2022;:271-274.
https://hdl.handle.net/21.15107/rcub_ibiss_5508 .

Čupić, Željko, Anić, Slobodan, Nikolić, Ljiljana, Vidović, Marija, Todorović, Nataša, Petković, Branka, Stojadinović, Gordana, Martać, Ljiljana, Bogdanović Pristov, Jelena, "Protoplast patch-clamping using an upright microscope with a movable stage" in Proceedings: Physical Chemistry 2022, Vol. 1.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia (2022):271-274,
https://hdl.handle.net/21.15107/rcub_ibiss_5508 .

TY  - CONF
AU  - Perić, Mina
AU  - Nikolić, Ljiljana
AU  - Bataveljić, Danijela
AU  - Andjus, Pavle
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5511
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by death of motor neurons in the spinal cord and brain. Non-neuronal cells particularly of glial origin play an essential role in disease onset and progression. The aim of our study was to examine functional properties of two glial species of the spinal cord, oligodendrocytes and microglia in the ALS SOD1G93A rat with a particular focus on the expression and functional significance of the inwardly rectifying potassium channel Kir4.1 that is abundantly expressed in these glial cells. 
We demonstrate that the expression of Kir4.1 is markedly diminished in oligodendrocytes of the SOD1G93A rat. Moreover, our data show an elevated number of dysmorphic oligodendrocytes, indicative of a degenerative phenotype. To assess physiological properties of oligodendrocytes, we prepared cell cultures from the rat spinal cord. The cells isolated from the SOD1G93A spinal cord displayed similar processes ramification as the control, but expressed a lower level of Kir4.1. Whole-cell patch-clamp recordings revealed compromised membrane biophysical properties and diminished inward currents in ALS oligodendrocytes, while the Ba2+-sensitive Kir current was decreased in ALS oligodendrocytes [1]. 
The microglia in the ALS rat spinal chords shows remarkable clustering in ventral horns, already starting in presymptomatic animals. Colocalization of Kir4.1 and microglial Iba1 staining was 2-3 times more abudant in presymptomatic as well as in symptomatic animals compared to individual cells. The morphology of micorglia also changes in ALS where the number and length of processes dicreases almost the same in pre- and symptomatic animals. It was also shown that these clusters bare a higher accumulation and colocalization with Kir4.1 and Iba1 of mutated SOD1 compared to individual cells. Similarly, the transmembrane marker of microglial fagocitosis, CD68 was also augmented in these clusters. 
The spinal chord micorglial cells were cultured and explored with patch-clamp electrophysiology by using an innovative movable microscope stage [2] to facilitate the gigaseal formation of the cell membrane and patch pipette. These measurements demonstrated a decrease of Kir Ba2+-sensitive currents.
Altogether, our findings provide the evidence of impaired Kir4.1 expression and function in SOD1G93A spinal cord oligodendrocytes and microglia with this channel’s particular abundance in clusters typical of ALS pathology and its progression.
REFERENCES
[1]	M.Peric, L. Nikolic L, et al. Eur J Neurosci. 54 (2021), 6339-6354.
[2]	M.Peric, D. Bataveljić et al. Microsc Res Tech. (2022) , DOI: 10.1002/jemt.24066
PB  - Belgrade: Institute of Physics
C3  - Book of Abstracts: 15th Photonics Workshop: Conference; 2022 Mar 13-16; Kopaonik, Serbia
T1  - Imaging the molecular markers of neurodegeneration in the ALS rat oligodendrocytes and microglia
SP  - 35
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5511
ER  - 

@conference{
author = "Perić, Mina and Nikolić, Ljiljana and Bataveljić, Danijela and Andjus, Pavle",
year = "2022",
abstract = "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by death of motor neurons in the spinal cord and brain. Non-neuronal cells particularly of glial origin play an essential role in disease onset and progression. The aim of our study was to examine functional properties of two glial species of the spinal cord, oligodendrocytes and microglia in the ALS SOD1G93A rat with a particular focus on the expression and functional significance of the inwardly rectifying potassium channel Kir4.1 that is abundantly expressed in these glial cells. 
We demonstrate that the expression of Kir4.1 is markedly diminished in oligodendrocytes of the SOD1G93A rat. Moreover, our data show an elevated number of dysmorphic oligodendrocytes, indicative of a degenerative phenotype. To assess physiological properties of oligodendrocytes, we prepared cell cultures from the rat spinal cord. The cells isolated from the SOD1G93A spinal cord displayed similar processes ramification as the control, but expressed a lower level of Kir4.1. Whole-cell patch-clamp recordings revealed compromised membrane biophysical properties and diminished inward currents in ALS oligodendrocytes, while the Ba2+-sensitive Kir current was decreased in ALS oligodendrocytes [1]. 
The microglia in the ALS rat spinal chords shows remarkable clustering in ventral horns, already starting in presymptomatic animals. Colocalization of Kir4.1 and microglial Iba1 staining was 2-3 times more abudant in presymptomatic as well as in symptomatic animals compared to individual cells. The morphology of micorglia also changes in ALS where the number and length of processes dicreases almost the same in pre- and symptomatic animals. It was also shown that these clusters bare a higher accumulation and colocalization with Kir4.1 and Iba1 of mutated SOD1 compared to individual cells. Similarly, the transmembrane marker of microglial fagocitosis, CD68 was also augmented in these clusters. 
The spinal chord micorglial cells were cultured and explored with patch-clamp electrophysiology by using an innovative movable microscope stage [2] to facilitate the gigaseal formation of the cell membrane and patch pipette. These measurements demonstrated a decrease of Kir Ba2+-sensitive currents.
Altogether, our findings provide the evidence of impaired Kir4.1 expression and function in SOD1G93A spinal cord oligodendrocytes and microglia with this channel’s particular abundance in clusters typical of ALS pathology and its progression.
REFERENCES
[1]	M.Peric, L. Nikolic L, et al. Eur J Neurosci. 54 (2021), 6339-6354.
[2]	M.Peric, D. Bataveljić et al. Microsc Res Tech. (2022) , DOI: 10.1002/jemt.24066",
publisher = "Belgrade: Institute of Physics",
journal = "Book of Abstracts: 15th Photonics Workshop: Conference; 2022 Mar 13-16; Kopaonik, Serbia",
title = "Imaging the molecular markers of neurodegeneration in the ALS rat oligodendrocytes and microglia",
pages = "35",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5511"
}

Perić, M., Nikolić, L., Bataveljić, D.,& Andjus, P.. (2022). Imaging the molecular markers of neurodegeneration in the ALS rat oligodendrocytes and microglia. in Book of Abstracts: 15th Photonics Workshop: Conference; 2022 Mar 13-16; Kopaonik, Serbia
Belgrade: Institute of Physics., 35.
https://hdl.handle.net/21.15107/rcub_ibiss_5511

Perić M, Nikolić L, Bataveljić D, Andjus P. Imaging the molecular markers of neurodegeneration in the ALS rat oligodendrocytes and microglia. in Book of Abstracts: 15th Photonics Workshop: Conference; 2022 Mar 13-16; Kopaonik, Serbia. 2022;:35.
https://hdl.handle.net/21.15107/rcub_ibiss_5511 .

Perić, Mina, Nikolić, Ljiljana, Bataveljić, Danijela, Andjus, Pavle, "Imaging the molecular markers of neurodegeneration in the ALS rat oligodendrocytes and microglia" in Book of Abstracts: 15th Photonics Workshop: Conference; 2022 Mar 13-16; Kopaonik, Serbia (2022):35,
https://hdl.handle.net/21.15107/rcub_ibiss_5511 .

TY  - CONF
AU  - Nikolić, Ljiljana
AU  - Savić, Danijela
AU  - Korać Jačić, Jelena
AU  - Petković, Branka
AU  - Stojadinović, Gordana
AU  - Martać, Ljiljana
AU  - Bogdanović Pristov, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5509
AB  - Living cells exhibit multiple ion channel proteins and malfunction of these channels underlies
numerous diseases. Channelopathies include diseases of the nervous, cardiovascular, respiratory,
endocrine, urinary, and immune system. Currently, ion channels represent the second-largest target
for existing drugs. Here, using the whole-cell patch-clamp technique, we explored the epinephrine
effect on membrane ionic currents in glioma C6 cells. We demonstrate that epinephrine specifically
evokes an increase of C6 cells outward ionic currents that is stable within 10 min, while it does not
affect inward currents. Our results thus provide fine resolution and time frame for targeting ion
channel activity that is crucial in pharmacological investigations.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: Physical Chemistry 2022, Vol. 2.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
T1  - Membrane currents of C6 cells in pharmacological investigation
SP  - 589
EP  - 592
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5509
ER  - 

@conference{
author = "Nikolić, Ljiljana and Savić, Danijela and Korać Jačić, Jelena and Petković, Branka and Stojadinović, Gordana and Martać, Ljiljana and Bogdanović Pristov, Jelena",
year = "2022",
abstract = "Living cells exhibit multiple ion channel proteins and malfunction of these channels underlies
numerous diseases. Channelopathies include diseases of the nervous, cardiovascular, respiratory,
endocrine, urinary, and immune system. Currently, ion channels represent the second-largest target
for existing drugs. Here, using the whole-cell patch-clamp technique, we explored the epinephrine
effect on membrane ionic currents in glioma C6 cells. We demonstrate that epinephrine specifically
evokes an increase of C6 cells outward ionic currents that is stable within 10 min, while it does not
affect inward currents. Our results thus provide fine resolution and time frame for targeting ion
channel activity that is crucial in pharmacological investigations.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: Physical Chemistry 2022, Vol. 2.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia",
title = "Membrane currents of C6 cells in pharmacological investigation",
pages = "589-592",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5509"
}

Nikolić, L., Savić, D., Korać Jačić, J., Petković, B., Stojadinović, G., Martać, L.,& Bogdanović Pristov, J.. (2022). Membrane currents of C6 cells in pharmacological investigation. in Proceedings: Physical Chemistry 2022, Vol. 2.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 589-592.
https://hdl.handle.net/21.15107/rcub_ibiss_5509

Nikolić L, Savić D, Korać Jačić J, Petković B, Stojadinović G, Martać L, Bogdanović Pristov J. Membrane currents of C6 cells in pharmacological investigation. in Proceedings: Physical Chemistry 2022, Vol. 2.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia. 2022;:589-592.
https://hdl.handle.net/21.15107/rcub_ibiss_5509 .

Nikolić, Ljiljana, Savić, Danijela, Korać Jačić, Jelena, Petković, Branka, Stojadinović, Gordana, Martać, Ljiljana, Bogdanović Pristov, Jelena, "Membrane currents of C6 cells in pharmacological investigation" in Proceedings: Physical Chemistry 2022, Vol. 2.: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry; 2022 Sep 26-30; Belgrade, Serbia (2022):589-592,
https://hdl.handle.net/21.15107/rcub_ibiss_5509 .

TY  - JOUR
AU  - Bogdanovic Pristov, Jelena
AU  - Nikolić, Ljiljana
PY  - 2021
UR  - http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=12;spage=2395;epage=2396;aulast=Bogdanovic
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4240
PB  - Wolters Kluwer Medknow Publications
T2  - Neural Regeneration Research
T1  - Light of the stars: calcium signals light up astrocytes in the presence of autoreactive CD4 + T cells
IS  - 12
VL  - 16
DO  - 10.4103/1673-5374.313036
SP  - 2395
ER  - 

@article{
author = "Bogdanovic Pristov, Jelena and Nikolić, Ljiljana",
year = "2021",
publisher = "Wolters Kluwer Medknow Publications",
journal = "Neural Regeneration Research",
title = "Light of the stars: calcium signals light up astrocytes in the presence of autoreactive CD4 + T cells",
number = "12",
volume = "16",
doi = "10.4103/1673-5374.313036",
pages = "2395"
}

Bogdanovic Pristov, J.,& Nikolić, L.. (2021). Light of the stars: calcium signals light up astrocytes in the presence of autoreactive CD4 + T cells. in Neural Regeneration Research
Wolters Kluwer Medknow Publications., 16(12), 2395.
https://doi.org/10.4103/1673-5374.313036

Bogdanovic Pristov J, Nikolić L. Light of the stars: calcium signals light up astrocytes in the presence of autoreactive CD4 + T cells. in Neural Regeneration Research. 2021;16(12):2395.
doi:10.4103/1673-5374.313036 .

Bogdanovic Pristov, Jelena, Nikolić, Ljiljana, "Light of the stars: calcium signals light up astrocytes in the presence of autoreactive CD4 + T cells" in Neural Regeneration Research, 16, no. 12 (2021):2395,
https://doi.org/10.4103/1673-5374.313036 . .

TY  - JOUR
AU  - Perić, Mina
AU  - Nikolić, Ljiljana
AU  - Anđus, Pavle R.
AU  - Bataveljić, Danijela
PY  - 2021
UR  - https://onlinelibrary.wiley.com/doi/10.1111/ejn.15451
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4486
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the death of motor neurons in the spinal cord and the brain. Although this disease is characterized by motoneuron degeneration, non-neuronal cells such as oligodendrocytes play an important role in the disease onset and progression. The aim of our study was to examine functional properties of oligodendrocytes in the SOD1G93A rat model of ALS with a particular focus on the inwardly rectifying potassium channel Kir4.1 that is abundantly expressed in these glial cells and plays a role in the regulation of extracellular K+ . First, we demonstrate that the expression of Kir4.1 is diminished in the spinal cord oligodendrocytes of the SOD1G93A rat. Moreover, our data show an elevated number of dysmorphic oligodendrocytes in the ALS spinal cord that is indicative of a degenerative phenotype. In order to assess physiological properties of oligodendrocytes, we prepared cell cultures from the rat spinal cord. Oligodendrocytes isolated from the SOD1G93A spinal cord display similar ramification of the processes as the control but express a lower level of Kir4.1. We further demonstrate an impairment of oligodendrocyte functional properties in ALS. Remarkably, whole-cell patch-clamp recordings revealed compromised membrane biophysical properties and diminished inward currents in the SOD1G93A oligodendrocytes. In addition, the Ba2+ -sensitive Kir currents were decreased in ALS oligodendrocytes. Altogether, our findings provide the evidence of impaired Kir4.1 expression and function in oligodendrocytes of the SOD1G93A spinal cord, suggesting oligodendrocyte Kir4.1 channel as a potential contributor to the ALS pathophysiology.
PB  - Hoboken: John Wiley and Sons Inc.
T2  - European Journal of Neuroscience
T1  - Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis.
IS  - 7
VL  - 54
DO  - 10.1111/ejn.15451
SP  - 6339
EP  - 6354
ER  - 

@article{
author = "Perić, Mina and Nikolić, Ljiljana and Anđus, Pavle R. and Bataveljić, Danijela",
year = "2021",
abstract = "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the death of motor neurons in the spinal cord and the brain. Although this disease is characterized by motoneuron degeneration, non-neuronal cells such as oligodendrocytes play an important role in the disease onset and progression. The aim of our study was to examine functional properties of oligodendrocytes in the SOD1G93A rat model of ALS with a particular focus on the inwardly rectifying potassium channel Kir4.1 that is abundantly expressed in these glial cells and plays a role in the regulation of extracellular K+ . First, we demonstrate that the expression of Kir4.1 is diminished in the spinal cord oligodendrocytes of the SOD1G93A rat. Moreover, our data show an elevated number of dysmorphic oligodendrocytes in the ALS spinal cord that is indicative of a degenerative phenotype. In order to assess physiological properties of oligodendrocytes, we prepared cell cultures from the rat spinal cord. Oligodendrocytes isolated from the SOD1G93A spinal cord display similar ramification of the processes as the control but express a lower level of Kir4.1. We further demonstrate an impairment of oligodendrocyte functional properties in ALS. Remarkably, whole-cell patch-clamp recordings revealed compromised membrane biophysical properties and diminished inward currents in the SOD1G93A oligodendrocytes. In addition, the Ba2+ -sensitive Kir currents were decreased in ALS oligodendrocytes. Altogether, our findings provide the evidence of impaired Kir4.1 expression and function in oligodendrocytes of the SOD1G93A spinal cord, suggesting oligodendrocyte Kir4.1 channel as a potential contributor to the ALS pathophysiology.",
publisher = "Hoboken: John Wiley and Sons Inc.",
journal = "European Journal of Neuroscience",
title = "Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis.",
number = "7",
volume = "54",
doi = "10.1111/ejn.15451",
pages = "6339-6354"
}

Perić, M., Nikolić, L., Anđus, P. R.,& Bataveljić, D.. (2021). Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis.. in European Journal of Neuroscience
Hoboken: John Wiley and Sons Inc.., 54(7), 6339-6354.
https://doi.org/10.1111/ejn.15451

Perić M, Nikolić L, Anđus PR, Bataveljić D. Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis.. in European Journal of Neuroscience. 2021;54(7):6339-6354.
doi:10.1111/ejn.15451 .

Perić, Mina, Nikolić, Ljiljana, Anđus, Pavle R., Bataveljić, Danijela, "Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis." in European Journal of Neuroscience, 54, no. 7 (2021):6339-6354,
https://doi.org/10.1111/ejn.15451 . .

TY  - JOUR
AU  - Bijelić, Dunja D.
AU  - Milićević, Katarina D.
AU  - Lazarević, Milica
AU  - Miljković, Đorđe
AU  - Bogdanović Pristov, Jelena J.
AU  - Savić, Danijela
AU  - Petković, Branka
AU  - Anđus, Pavle R.
AU  - Momčilović, Miljana
AU  - Nikolić, Ljiljana
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24699
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32799373
UR  - https://radar.ibiss.bg.ac.rs/123456789/3859
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4006
AB  - Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.
PB  - John Wiley and Sons Inc.
T2  - Journal of Neuroscience Research
T1  - Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling
IS  - 11
VL  - 98
DO  - 10.1002/jnr.24699
SP  - 2317
EP  - 2332
ER  - 

@article{
author = "Bijelić, Dunja D. and Milićević, Katarina D. and Lazarević, Milica and Miljković, Đorđe and Bogdanović Pristov, Jelena J. and Savić, Danijela and Petković, Branka and Anđus, Pavle R. and Momčilović, Miljana and Nikolić, Ljiljana",
year = "2020",
abstract = "Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.",
publisher = "John Wiley and Sons Inc.",
journal = "Journal of Neuroscience Research",
title = "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling",
number = "11",
volume = "98",
doi = "10.1002/jnr.24699",
pages = "2317-2332"
}

Bijelić, D. D., Milićević, K. D., Lazarević, M., Miljković, Đ., Bogdanović Pristov, J. J., Savić, D., Petković, B., Anđus, P. R., Momčilović, M.,& Nikolić, L.. (2020). Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research
John Wiley and Sons Inc.., 98(11), 2317-2332.
https://doi.org/10.1002/jnr.24699

Bijelić DD, Milićević KD, Lazarević M, Miljković Đ, Bogdanović Pristov JJ, Savić D, Petković B, Anđus PR, Momčilović M, Nikolić L. Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research. 2020;98(11):2317-2332.
doi:10.1002/jnr.24699 .

Bijelić, Dunja D., Milićević, Katarina D., Lazarević, Milica, Miljković, Đorđe, Bogdanović Pristov, Jelena J., Savić, Danijela, Petković, Branka, Anđus, Pavle R., Momčilović, Miljana, Nikolić, Ljiljana, "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling" in Journal of Neuroscience Research, 98, no. 11 (2020):2317-2332,
https://doi.org/10.1002/jnr.24699 . .

TY  - JOUR
AU  - Bijelić, Dunja D.
AU  - Milićević, Katarina D.
AU  - Lazarević, Milica
AU  - Miljković, Đorđe
AU  - Bogdanović Pristov, Jelena J.
AU  - Savić, Danijela
AU  - Petković, Branka
AU  - Anđus, Pavle R.
AU  - Momčilović, Miljana
AU  - Nikolić, Ljiljana
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24699
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32799373
UR  - https://radar.ibiss.bg.ac.rs/123456789/3859
AB  - Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.
PB  - John Wiley and Sons Inc.
T2  - Journal of Neuroscience Research
T1  - Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling
IS  - 11
VL  - 98
DO  - 10.1002/jnr.24699
SP  - 2317
EP  - 2332
ER  - 

@article{
author = "Bijelić, Dunja D. and Milićević, Katarina D. and Lazarević, Milica and Miljković, Đorđe and Bogdanović Pristov, Jelena J. and Savić, Danijela and Petković, Branka and Anđus, Pavle R. and Momčilović, Miljana and Nikolić, Ljiljana",
year = "2020",
abstract = "Interaction between autoreactive immune cells and astroglia is an important part of the pathologic processes that fuel neurodegeneration in multiple sclerosis. In this inflammatory disease, immune cells enter into the central nervous system (CNS) and they spread through CNS parenchyma, but the impact of these autoreactive immune cells on the activity pattern of astrocytes has not been defined. By exploiting naïve astrocytes in culture and CNS-infiltrated immune cells (CNS IICs) isolated from rat with experimental autoimmune encephalomyelitis (EAE), here we demonstrate previously unrecognized properties of immune cell-astrocyte interaction. We show that CNS IICs but not the peripheral immune cell application, evokes a rapid and vigorous intracellular Ca2+ increase in astrocytes by promoting glial release of ATP. ATP propagated Ca2+ elevation through glial purinergic P2X7 receptor activation by the hemichannel-dependent nucleotide release mechanism. Astrocyte Ca2+ increase is specifically triggered by the autoreactive CD4+ T-cell application and these two cell types exhibit close spatial interaction in EAE. Therefore, Ca2+ signals may mediate a rapid astroglial response to the autoreactive immune cells in their local environment. This property of immune cell-astrocyte interaction may be important to consider in studies interrogating CNS autoimmune disease.",
publisher = "John Wiley and Sons Inc.",
journal = "Journal of Neuroscience Research",
title = "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling",
number = "11",
volume = "98",
doi = "10.1002/jnr.24699",
pages = "2317-2332"
}

Bijelić, D. D., Milićević, K. D., Lazarević, M., Miljković, Đ., Bogdanović Pristov, J. J., Savić, D., Petković, B., Anđus, P. R., Momčilović, M.,& Nikolić, L.. (2020). Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research
John Wiley and Sons Inc.., 98(11), 2317-2332.
https://doi.org/10.1002/jnr.24699

Bijelić DD, Milićević KD, Lazarević M, Miljković Đ, Bogdanović Pristov JJ, Savić D, Petković B, Anđus PR, Momčilović M, Nikolić L. Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling. in Journal of Neuroscience Research. 2020;98(11):2317-2332.
doi:10.1002/jnr.24699 .

Bijelić, Dunja D., Milićević, Katarina D., Lazarević, Milica, Miljković, Đorđe, Bogdanović Pristov, Jelena J., Savić, Danijela, Petković, Branka, Anđus, Pavle R., Momčilović, Miljana, Nikolić, Ljiljana, "Central nervous system-infiltrated immune cells induce calcium increase in astrocytes via astroglial purinergic signaling" in Journal of Neuroscience Research, 98, no. 11 (2020):2317-2332,
https://doi.org/10.1002/jnr.24699 . .

TY  - CONF
AU  - Perić, Mina
AU  - Nikolić, Ljiljana
AU  - Anđus, Pavle R.
AU  - Bataveljić, Danijela
PY  - 2020
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5499
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting lower
and upper motor neurons, leading to muscle atrophy, paralysis and death. Although
ALS is characterized by motoneuron degeneration, non-neuronal cells such as
oligodendrocytes play an essential role in disease onset and progression. The aim
of this study was to investigate functional properties of oligodendrocytes in the ALS
with particular focus on their role in the regulation of extracellular K+ through inwardly
rectifying potassium channel Kir4.1 abundantly expressed in these glial cells. We
employed immunolabeling of Kir4.1, and oligodendrocyte-specific marker CNPase,
to examine the expression of Kir4.1 in oligodendrocytes of the lumbar spinal cord of
SOD1G93A rat model of ALS. Furthermore, whole-cell patch-clamp recordings were
performed on primary oligodendrocyte cultures from ALS and control rats to
investigate functional properties of these cells. Our data show reduced expression
of Kir4.1 in the oligodendrocytes in the lumbar spinal cord of SOD1G93A rat compared
to control. Moreover, we found elevated number of dysmorphic oligodendrocytes in
the ALS spinal cord, indicative of a degenerative phenotype. Oligodendrocytes
isolated from SOD1G93A spinal cord display similar processes ramification as the
control, however expressing a lower level of Kir4.1. Electrophysiological examination
of cultured SOD1G93A oligodendrocytes revealed compromised membrane
properties and diminished inward currents in comparison to control. In addition, the
Ba2+-sensitive Kir current is decreased in ALS oligodendrocytes. Altogether, our
findings provide the evidence of impaired Kir4.1 expression and function in
SOD1G93A spinal cord oligodendrocytes suggesting a critical role of oligodendrocyte
Kir4.1 channel in ALS pathophysiology.
PB  - Querétaro, México: Instituto de neurobiologia
C3  - Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual
T1  - Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis
SP  - 75
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5499
ER  - 

@conference{
author = "Perić, Mina and Nikolić, Ljiljana and Anđus, Pavle R. and Bataveljić, Danijela",
year = "2020",
abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting lower
and upper motor neurons, leading to muscle atrophy, paralysis and death. Although
ALS is characterized by motoneuron degeneration, non-neuronal cells such as
oligodendrocytes play an essential role in disease onset and progression. The aim
of this study was to investigate functional properties of oligodendrocytes in the ALS
with particular focus on their role in the regulation of extracellular K+ through inwardly
rectifying potassium channel Kir4.1 abundantly expressed in these glial cells. We
employed immunolabeling of Kir4.1, and oligodendrocyte-specific marker CNPase,
to examine the expression of Kir4.1 in oligodendrocytes of the lumbar spinal cord of
SOD1G93A rat model of ALS. Furthermore, whole-cell patch-clamp recordings were
performed on primary oligodendrocyte cultures from ALS and control rats to
investigate functional properties of these cells. Our data show reduced expression
of Kir4.1 in the oligodendrocytes in the lumbar spinal cord of SOD1G93A rat compared
to control. Moreover, we found elevated number of dysmorphic oligodendrocytes in
the ALS spinal cord, indicative of a degenerative phenotype. Oligodendrocytes
isolated from SOD1G93A spinal cord display similar processes ramification as the
control, however expressing a lower level of Kir4.1. Electrophysiological examination
of cultured SOD1G93A oligodendrocytes revealed compromised membrane
properties and diminished inward currents in comparison to control. In addition, the
Ba2+-sensitive Kir current is decreased in ALS oligodendrocytes. Altogether, our
findings provide the evidence of impaired Kir4.1 expression and function in
SOD1G93A spinal cord oligodendrocytes suggesting a critical role of oligodendrocyte
Kir4.1 channel in ALS pathophysiology.",
publisher = "Querétaro, México: Instituto de neurobiologia",
journal = "Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual",
title = "Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis",
pages = "75",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5499"
}

Perić, M., Nikolić, L., Anđus, P. R.,& Bataveljić, D.. (2020). Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual
Querétaro, México: Instituto de neurobiologia., 75.
https://hdl.handle.net/21.15107/rcub_ibiss_5499

Perić M, Nikolić L, Anđus PR, Bataveljić D. Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. 2020;:75.
https://hdl.handle.net/21.15107/rcub_ibiss_5499 .

Perić, Mina, Nikolić, Ljiljana, Anđus, Pavle R., Bataveljić, Danijela, "Dysfunction of oligodendrocyte inwardly rectifying potassium channel in a rat model of amyotrophic lateral sclerosis" in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual (2020):75,
https://hdl.handle.net/21.15107/rcub_ibiss_5499 .

TY  - CONF
AU  - Milićević, Katarina
AU  - Bijelić, Dunja
AU  - Lazarević, Milica
AU  - Miljković, Đorđe
AU  - Bogdanović Pristov, Jelena
AU  - Petković, Branka
AU  - Anđus, Pavle
AU  - Momčilović, Miljana
AU  - Nikolić, Ljiljana
PY  - 2020
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5514
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS), characterized by focal neurodegenerative and demyelinating lesions.
A major contributor to the pathogenic process of MS is the complex interaction
between astrocytes and the CNS-infiltrating immune cells (CNS-IIC). The aim of our
study is to explore how naïve astrocytes respond to the autoreactive immune cells
that invade the CNS. For this reason, CNS-IICs were isolated and purified from
spinal cords of rats with experimental autoimmune encephalomyelitis. Ca2+
dynamics was monitored in Fluo-4 labeled naïve astrocytes, isolated from spinal
cords of wild type rat pups, following brief bath application of CNS-IIC or peripheral
immune cells, with different pharmacological agents. CNS-IICs, and not peripheral
immune cells, induced robust elevation of intracellular Ca2+ in naïve astrocytes. We
demonstrated that this CNS IIC-induced increase in astrocyte Ca2+ does not depend
on the metabotropic glutamate receptors, metabotropic purinergic P2Y1 receptors
or TRPA1 channels. Remarkably, further research showed that Ca2+ elevation in
astrocytes upon exposure to CNS IICs is due to the activation of ionotropic purinergic
P2X7 receptors. Bioluminescence assay showed that immune cell-derived ATP is
not a cause of astrocytic P2X7 receptor activation. In fact, we showed that CNS-IICs
promoted P2X7 receptor activation and increase in cytosolic Ca2+ in astrocytes by
astrocytic hemichannel-dependent ATP release mechanism. Our data suggest that
direct contact between astrocytes and CNS IICs induce ATP-dependent Ca2+
changes in astrocytes and points to the new aspect of cell-cell interactions in
propagation of neuroinflammatory response in CNS autoimmunity.
PB  - Querétaro, México: Instituto de neurobiologia
C3  - Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual
T1  - Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes
SP  - 45
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5514
ER  - 

@conference{
author = "Milićević, Katarina and Bijelić, Dunja and Lazarević, Milica and Miljković, Đorđe and Bogdanović Pristov, Jelena and Petković, Branka and Anđus, Pavle and Momčilović, Miljana and Nikolić, Ljiljana",
year = "2020",
abstract = "Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS), characterized by focal neurodegenerative and demyelinating lesions.
A major contributor to the pathogenic process of MS is the complex interaction
between astrocytes and the CNS-infiltrating immune cells (CNS-IIC). The aim of our
study is to explore how naïve astrocytes respond to the autoreactive immune cells
that invade the CNS. For this reason, CNS-IICs were isolated and purified from
spinal cords of rats with experimental autoimmune encephalomyelitis. Ca2+
dynamics was monitored in Fluo-4 labeled naïve astrocytes, isolated from spinal
cords of wild type rat pups, following brief bath application of CNS-IIC or peripheral
immune cells, with different pharmacological agents. CNS-IICs, and not peripheral
immune cells, induced robust elevation of intracellular Ca2+ in naïve astrocytes. We
demonstrated that this CNS IIC-induced increase in astrocyte Ca2+ does not depend
on the metabotropic glutamate receptors, metabotropic purinergic P2Y1 receptors
or TRPA1 channels. Remarkably, further research showed that Ca2+ elevation in
astrocytes upon exposure to CNS IICs is due to the activation of ionotropic purinergic
P2X7 receptors. Bioluminescence assay showed that immune cell-derived ATP is
not a cause of astrocytic P2X7 receptor activation. In fact, we showed that CNS-IICs
promoted P2X7 receptor activation and increase in cytosolic Ca2+ in astrocytes by
astrocytic hemichannel-dependent ATP release mechanism. Our data suggest that
direct contact between astrocytes and CNS IICs induce ATP-dependent Ca2+
changes in astrocytes and points to the new aspect of cell-cell interactions in
propagation of neuroinflammatory response in CNS autoimmunity.",
publisher = "Querétaro, México: Instituto de neurobiologia",
journal = "Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual",
title = "Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes",
pages = "45",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5514"
}

Milićević, K., Bijelić, D., Lazarević, M., Miljković, Đ., Bogdanović Pristov, J., Petković, B., Anđus, P., Momčilović, M.,& Nikolić, L.. (2020). Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual
Querétaro, México: Instituto de neurobiologia., 45.
https://hdl.handle.net/21.15107/rcub_ibiss_5514

Milićević K, Bijelić D, Lazarević M, Miljković Đ, Bogdanović Pristov J, Petković B, Anđus P, Momčilović M, Nikolić L. Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes. in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual. 2020;:45.
https://hdl.handle.net/21.15107/rcub_ibiss_5514 .

Milićević, Katarina, Bijelić, Dunja, Lazarević, Milica, Miljković, Đorđe, Bogdanović Pristov, Jelena, Petković, Branka, Anđus, Pavle, Momčilović, Miljana, Nikolić, Ljiljana, "Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes" in Proceedings: 3rd Symposium on Physiology and pathology of neuroglia; 2020 Noc 24-25; Virtual (2020):45,
https://hdl.handle.net/21.15107/rcub_ibiss_5514 .

TY  - JOUR
AU  - Nikolić, Ljiljana
AU  - Nobili, Paola
AU  - Shen, Weida
AU  - Audinat, Etienne
PY  - 2020
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23747
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3525
AB  - Epilepsy is characterized by unpredictable recurrent seizures resulting from hypersynchronous discharges from neuron assemblies. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability. Purinergic signaling is central in neuron-glia and glia-glia interactions and dysfunctions in communication pathways involving purinergic receptors have been reported in various CNS pathologies, such as Alzheimer disease, stroke, major depression, schizophrenia, and epilepsy. In the present review we will first discuss the mechanisms by which astrocytes influence neuronal activity. We will then review in more details recent evidence indicating that dysregulation of astrocyte purinergic signaling actively contributes to the appearance of abnormal neuronal activity in epilepsy.
T2  - Glia
T1  - Role of astrocyte purinergic signaling in epilepsy.
IS  - 9
VL  - 68
DO  - 10.1002/glia.23747
SP  - 1677
EP  - 1691
ER  - 

@article{
author = "Nikolić, Ljiljana and Nobili, Paola and Shen, Weida and Audinat, Etienne",
year = "2020",
abstract = "Epilepsy is characterized by unpredictable recurrent seizures resulting from hypersynchronous discharges from neuron assemblies. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability. Purinergic signaling is central in neuron-glia and glia-glia interactions and dysfunctions in communication pathways involving purinergic receptors have been reported in various CNS pathologies, such as Alzheimer disease, stroke, major depression, schizophrenia, and epilepsy. In the present review we will first discuss the mechanisms by which astrocytes influence neuronal activity. We will then review in more details recent evidence indicating that dysregulation of astrocyte purinergic signaling actively contributes to the appearance of abnormal neuronal activity in epilepsy.",
journal = "Glia",
title = "Role of astrocyte purinergic signaling in epilepsy.",
number = "9",
volume = "68",
doi = "10.1002/glia.23747",
pages = "1677-1691"
}

Nikolić, L., Nobili, P., Shen, W.,& Audinat, E.. (2020). Role of astrocyte purinergic signaling in epilepsy.. in Glia, 68(9), 1677-1691.
https://doi.org/10.1002/glia.23747

Nikolić L, Nobili P, Shen W, Audinat E. Role of astrocyte purinergic signaling in epilepsy.. in Glia. 2020;68(9):1677-1691.
doi:10.1002/glia.23747 .

Nikolić, Ljiljana, Nobili, Paola, Shen, Weida, Audinat, Etienne, "Role of astrocyte purinergic signaling in epilepsy." in Glia, 68, no. 9 (2020):1677-1691,
https://doi.org/10.1002/glia.23747 . .

TY  - JOUR
AU  - Korać Jačić, Jelena
AU  - Nikolić, Ljiljana
AU  - Stanković, Dalibor M.
AU  - Opačić, Miloš
AU  - Dimitrijević, Milena
AU  - Savić, Danijela
AU  - Grgurić Šipka, Sanja
AU  - Spasojević, Ivan
AU  - Bogdanović Pristov, Jelena
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3597
AB  - Upon release in response to stress, epinephrine (Epi) may interact with labile iron pool in human plasma with potentially important (patho)physiological consequences. We have shown that Epi and Fe3+ build stable 1:1 high-spin bidentate complex at physiological pH, and that Epi does not undergo degradation in the presence of iron. However, the interactions of Epi with the more soluble Fe2+, and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe2+ build colorless complex which is stable under anaerobic conditions. In the presence of O2, Epi promoted the oxidation of Fe2+ and the formation of Epi-Fe3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe2+ complex is very low (-582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe2+. Next, we examined the impact of iron binding on biological performance of Epi using patch clamping in cell culture with constitutive expression of adrenergic receptors. Epi alone evoked an increase of outward currents, whereas Epi in the complex with Fe3+ did not. This implies that the binding of Epi to adrenergic receptors and their activation is prevented by the formation of complex with iron. Pro-oxidative activity of Epi-Fe2+ complex may represent a link between chronic stress and cardiovascular problems. On the other hand, labile iron could serve as a modulator of biological activity of ligands. Such interactions may be important in human pathologies that are related to iron overload or deficiency.
T2  - Free Radical Biology and Medicine
T1  - Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.
VL  - 148
DO  - 10.1016/j.freeradbiomed.2020.01.001
SP  - 123
EP  - 127
ER  - 

@article{
author = "Korać Jačić, Jelena and Nikolić, Ljiljana and Stanković, Dalibor M. and Opačić, Miloš and Dimitrijević, Milena and Savić, Danijela and Grgurić Šipka, Sanja and Spasojević, Ivan and Bogdanović Pristov, Jelena",
year = "2020",
abstract = "Upon release in response to stress, epinephrine (Epi) may interact with labile iron pool in human plasma with potentially important (patho)physiological consequences. We have shown that Epi and Fe3+ build stable 1:1 high-spin bidentate complex at physiological pH, and that Epi does not undergo degradation in the presence of iron. However, the interactions of Epi with the more soluble Fe2+, and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe2+ build colorless complex which is stable under anaerobic conditions. In the presence of O2, Epi promoted the oxidation of Fe2+ and the formation of Epi-Fe3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe2+ complex is very low (-582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe2+. Next, we examined the impact of iron binding on biological performance of Epi using patch clamping in cell culture with constitutive expression of adrenergic receptors. Epi alone evoked an increase of outward currents, whereas Epi in the complex with Fe3+ did not. This implies that the binding of Epi to adrenergic receptors and their activation is prevented by the formation of complex with iron. Pro-oxidative activity of Epi-Fe2+ complex may represent a link between chronic stress and cardiovascular problems. On the other hand, labile iron could serve as a modulator of biological activity of ligands. Such interactions may be important in human pathologies that are related to iron overload or deficiency.",
journal = "Free Radical Biology and Medicine",
title = "Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.",
volume = "148",
doi = "10.1016/j.freeradbiomed.2020.01.001",
pages = "123-127"
}

Korać Jačić, J., Nikolić, L., Stanković, D. M., Opačić, M., Dimitrijević, M., Savić, D., Grgurić Šipka, S., Spasojević, I.,& Bogdanović Pristov, J.. (2020). Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.. in Free Radical Biology and Medicine, 148, 123-127.
https://doi.org/10.1016/j.freeradbiomed.2020.01.001

Korać Jačić J, Nikolić L, Stanković DM, Opačić M, Dimitrijević M, Savić D, Grgurić Šipka S, Spasojević I, Bogdanović Pristov J. Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors.. in Free Radical Biology and Medicine. 2020;148:123-127.
doi:10.1016/j.freeradbiomed.2020.01.001 .

Korać Jačić, Jelena, Nikolić, Ljiljana, Stanković, Dalibor M., Opačić, Miloš, Dimitrijević, Milena, Savić, Danijela, Grgurić Šipka, Sanja, Spasojević, Ivan, Bogdanović Pristov, Jelena, "Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors." in Free Radical Biology and Medicine, 148 (2020):123-127,
https://doi.org/10.1016/j.freeradbiomed.2020.01.001 . .

TY  - CONF
AU  - Nikolić, Ljiljana
AU  - Korać, Jelena
AU  - Bijelić, Dunja
AU  - Spasojević, Ivan
AU  - Bogdanović Pristov, Jelena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5510
AB  - Iron, an essential element for living organisms, participates in a wide range of metabolic
processes. It appears predominantly firmly bound to proteins, but can also be loosely bound to
low-affinity ligands, referred as labile iron pool (LIP). The composition and amount of LIP can
vary considerably under different physiological conditions, playing a beneficial role in iron
economy and homeostasis or contributing to the generation of reactive oxygen species. It is
still not known if bioactivity of low-affinity ligands can be modulated by iron binding.
Catecholamine neurotransmitters including norepinephrine (NE) can chelate iron. In the close
vicinity of synaptic cleft, astrocytes are direct target of norepinephrine. Here we show on
cultured rat cortical astrocytes that iron bound to NE completely blocks neurotransmitter
activity of NE. However, how astrocyte activity changes when norepinephrine binds iron
remains unknown.
We show, using spectrophotometry that NE and Fe3+ form complex in the 1:1 stoichiometry,
at pH 7.4. Iron effect on astrocyte response to NE was examined by the whole-cell patch-clamp
technique. NE alone evokes changes in the membrane currents of astrocytes, but such effects
were not observed for the NE- Fe3+ complex.
Our results demonstrating that iron in the complex with norepinephrine inhibits alpha-adrenergic
receptors and modulates astrocyte activity, imply a novel neuromodulatory role for LIP.
PB  - COST Action CA15133
C3  - Book of abstracts: 4th FeSBioNet Meeting: COST Action CA15133; 2019 Sep 16-19; Gdansk, Poland
T1  - Iron modulates norepinephrine effect on astrocytes
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5510
ER  - 

@conference{
author = "Nikolić, Ljiljana and Korać, Jelena and Bijelić, Dunja and Spasojević, Ivan and Bogdanović Pristov, Jelena",
year = "2019",
abstract = "Iron, an essential element for living organisms, participates in a wide range of metabolic
processes. It appears predominantly firmly bound to proteins, but can also be loosely bound to
low-affinity ligands, referred as labile iron pool (LIP). The composition and amount of LIP can
vary considerably under different physiological conditions, playing a beneficial role in iron
economy and homeostasis or contributing to the generation of reactive oxygen species. It is
still not known if bioactivity of low-affinity ligands can be modulated by iron binding.
Catecholamine neurotransmitters including norepinephrine (NE) can chelate iron. In the close
vicinity of synaptic cleft, astrocytes are direct target of norepinephrine. Here we show on
cultured rat cortical astrocytes that iron bound to NE completely blocks neurotransmitter
activity of NE. However, how astrocyte activity changes when norepinephrine binds iron
remains unknown.
We show, using spectrophotometry that NE and Fe3+ form complex in the 1:1 stoichiometry,
at pH 7.4. Iron effect on astrocyte response to NE was examined by the whole-cell patch-clamp
technique. NE alone evokes changes in the membrane currents of astrocytes, but such effects
were not observed for the NE- Fe3+ complex.
Our results demonstrating that iron in the complex with norepinephrine inhibits alpha-adrenergic
receptors and modulates astrocyte activity, imply a novel neuromodulatory role for LIP.",
publisher = "COST Action CA15133",
journal = "Book of abstracts: 4th FeSBioNet Meeting: COST Action CA15133; 2019 Sep 16-19; Gdansk, Poland",
title = "Iron modulates norepinephrine effect on astrocytes",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5510"
}

Nikolić, L., Korać, J., Bijelić, D., Spasojević, I.,& Bogdanović Pristov, J.. (2019). Iron modulates norepinephrine effect on astrocytes. in Book of abstracts: 4th FeSBioNet Meeting: COST Action CA15133; 2019 Sep 16-19; Gdansk, Poland
COST Action CA15133..
https://hdl.handle.net/21.15107/rcub_ibiss_5510

Nikolić L, Korać J, Bijelić D, Spasojević I, Bogdanović Pristov J. Iron modulates norepinephrine effect on astrocytes. in Book of abstracts: 4th FeSBioNet Meeting: COST Action CA15133; 2019 Sep 16-19; Gdansk, Poland. 2019;.
https://hdl.handle.net/21.15107/rcub_ibiss_5510 .

Nikolić, Ljiljana, Korać, Jelena, Bijelić, Dunja, Spasojević, Ivan, Bogdanović Pristov, Jelena, "Iron modulates norepinephrine effect on astrocytes" in Book of abstracts: 4th FeSBioNet Meeting: COST Action CA15133; 2019 Sep 16-19; Gdansk, Poland (2019),
https://hdl.handle.net/21.15107/rcub_ibiss_5510 .

TY  - CONF
AU  - Nikolić, Ljiljana
AU  - Bijelić, Dunja
AU  - Lazarević, Milica
AU  - Milićević, Katarina
AU  - Momčilović, Miljana
AU  - Bogdanović Pristov, Jelena
AU  - Petković, Branka
AU  - Anđus, Pavle
AU  - Miljković, Đorđe
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5500
AB  - Aims: Multiple sclerosis (MS) is an in ammatory autoimmune disorder of the central nervous system (CNS). Complex
interactions between in ltrating immune cells (IIC) and resident glial cells of the CNS cause myelin loss and neuronal dysfunction
in MS. Here we aim to understand how naïve astrocytes functionally respond to the IIC invasion of the CNS.
Methods: We measured calcium activity of naïve astrocytes in culture upon application of IIC. An experimental autoimmune
encephalomyelitis (EAE) MS rat model was used to isolate IIC from the spinal cord of animals at the symptomatic stage. Naïve
astrocytes were isolated from the spinal cord of WT rats.
Results: We show that IIC and not the lymph node immune cells evoke vigorous increase in the astrocyte calcium activity.
This IIC-induced calcium response depends on an autocrine activation of the purinergic P2X7 receptors on the naïve astrocytes.
We also show that IIC induce ATP release from astrocytes by a mechanism that involves gap junctions and/or hemichannels
activation and not the vesicular pathway. Our data indicate that ATP release and subsequent increase in the astrocytic calcium
activity mainly depends on the cell-cell contact between naïve astrocytes and IIC.
Conclusions: These results show that naïve astrocytes functionally respond to the IIC by augmented release of ATP. An increase
in ATP release would alter astrocyte-neuron communication and a ect neuronal function in MS.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Astrocyte activity in the central nervous system autoimmunity
SP  - 295
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5500
ER  - 

@conference{
author = "Nikolić, Ljiljana and Bijelić, Dunja and Lazarević, Milica and Milićević, Katarina and Momčilović, Miljana and Bogdanović Pristov, Jelena and Petković, Branka and Anđus, Pavle and Miljković, Đorđe",
year = "2019",
abstract = "Aims: Multiple sclerosis (MS) is an in ammatory autoimmune disorder of the central nervous system (CNS). Complex
interactions between in ltrating immune cells (IIC) and resident glial cells of the CNS cause myelin loss and neuronal dysfunction
in MS. Here we aim to understand how naïve astrocytes functionally respond to the IIC invasion of the CNS.
Methods: We measured calcium activity of naïve astrocytes in culture upon application of IIC. An experimental autoimmune
encephalomyelitis (EAE) MS rat model was used to isolate IIC from the spinal cord of animals at the symptomatic stage. Naïve
astrocytes were isolated from the spinal cord of WT rats.
Results: We show that IIC and not the lymph node immune cells evoke vigorous increase in the astrocyte calcium activity.
This IIC-induced calcium response depends on an autocrine activation of the purinergic P2X7 receptors on the naïve astrocytes.
We also show that IIC induce ATP release from astrocytes by a mechanism that involves gap junctions and/or hemichannels
activation and not the vesicular pathway. Our data indicate that ATP release and subsequent increase in the astrocytic calcium
activity mainly depends on the cell-cell contact between naïve astrocytes and IIC.
Conclusions: These results show that naïve astrocytes functionally respond to the IIC by augmented release of ATP. An increase
in ATP release would alter astrocyte-neuron communication and a ect neuronal function in MS.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Astrocyte activity in the central nervous system autoimmunity",
pages = "295",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5500"
}

Nikolić, L., Bijelić, D., Lazarević, M., Milićević, K., Momčilović, M., Bogdanović Pristov, J., Petković, B., Anđus, P.,& Miljković, Đ.. (2019). Astrocyte activity in the central nervous system autoimmunity. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 295.
https://hdl.handle.net/21.15107/rcub_ibiss_5500

Nikolić L, Bijelić D, Lazarević M, Milićević K, Momčilović M, Bogdanović Pristov J, Petković B, Anđus P, Miljković Đ. Astrocyte activity in the central nervous system autoimmunity. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:295.
https://hdl.handle.net/21.15107/rcub_ibiss_5500 .

Nikolić, Ljiljana, Bijelić, Dunja, Lazarević, Milica, Milićević, Katarina, Momčilović, Miljana, Bogdanović Pristov, Jelena, Petković, Branka, Anđus, Pavle, Miljković, Đorđe, "Astrocyte activity in the central nervous system autoimmunity" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):295,
https://hdl.handle.net/21.15107/rcub_ibiss_5500 .

TY  - CONF
AU  - Korać, Jelena
AU  - Nikolić, Ljiljana
AU  - Bijelić, Dunja
AU  - Spasojević, Ivan
AU  - Bogdanović Pristov, Jelena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5501
AB  - Aims: Astrocyte position between synapses and blood vessels allows them to ful l crucial functions such as regulation of
synaptic activity and potassium bu ering. Well positioned in the close vicinity of synaptic cleft astrocytes are considered to be
a direct target of norepinephrine (NE). Synaptic activity and neurotransmitter actions can be in uenced by extracellular iron.
Here we investigated whether iron interacts with NE and if this interaction can modulate astrocyte response to NE.
Methods: To investigate the interaction between iron and norepinephrine we used spectrophotometry approach. Iron e ect
on astrocyte response to NE was examined by the whole-cell patch-clamp technique. Membrane currents were recorded from
cultured cortical astrocytes prepared from WT rats.
Results: Using spectrophotometry we observed that iron interacts with NE which leads to the formation of a stable complex
in the 1:1 stoichiometry. We also found that iron bound to NE completely blocks NE-induced increase of large-conductance
calcium sensitive potassium current in astrocytes.
Conclusions: Astrocyte response to NE is modi ed when this neurotransmitter forms a complex with iron. This implies that
NE binding to astrocytic noradrenergic receptors may be prevented by iron. Our  ndings point toward compromised astrocyte
functions related to the potassium bu ering when NE action is modi ed by iron.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Iron modulates norepinephrine effect on astrocytes
SP  - 370
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5501
ER  - 

@conference{
author = "Korać, Jelena and Nikolić, Ljiljana and Bijelić, Dunja and Spasojević, Ivan and Bogdanović Pristov, Jelena",
year = "2019",
abstract = "Aims: Astrocyte position between synapses and blood vessels allows them to ful l crucial functions such as regulation of
synaptic activity and potassium bu ering. Well positioned in the close vicinity of synaptic cleft astrocytes are considered to be
a direct target of norepinephrine (NE). Synaptic activity and neurotransmitter actions can be in uenced by extracellular iron.
Here we investigated whether iron interacts with NE and if this interaction can modulate astrocyte response to NE.
Methods: To investigate the interaction between iron and norepinephrine we used spectrophotometry approach. Iron e ect
on astrocyte response to NE was examined by the whole-cell patch-clamp technique. Membrane currents were recorded from
cultured cortical astrocytes prepared from WT rats.
Results: Using spectrophotometry we observed that iron interacts with NE which leads to the formation of a stable complex
in the 1:1 stoichiometry. We also found that iron bound to NE completely blocks NE-induced increase of large-conductance
calcium sensitive potassium current in astrocytes.
Conclusions: Astrocyte response to NE is modi ed when this neurotransmitter forms a complex with iron. This implies that
NE binding to astrocytic noradrenergic receptors may be prevented by iron. Our  ndings point toward compromised astrocyte
functions related to the potassium bu ering when NE action is modi ed by iron.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Iron modulates norepinephrine effect on astrocytes",
pages = "370",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5501"
}

Korać, J., Nikolić, L., Bijelić, D., Spasojević, I.,& Bogdanović Pristov, J.. (2019). Iron modulates norepinephrine effect on astrocytes. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 370.
https://hdl.handle.net/21.15107/rcub_ibiss_5501

Korać J, Nikolić L, Bijelić D, Spasojević I, Bogdanović Pristov J. Iron modulates norepinephrine effect on astrocytes. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:370.
https://hdl.handle.net/21.15107/rcub_ibiss_5501 .

Korać, Jelena, Nikolić, Ljiljana, Bijelić, Dunja, Spasojević, Ivan, Bogdanović Pristov, Jelena, "Iron modulates norepinephrine effect on astrocytes" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):370,
https://hdl.handle.net/21.15107/rcub_ibiss_5501 .