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  - 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  - 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  - 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  - 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  - JOUR
AU  - Milošević, Milena
AU  - Milićević, Katarina
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Bijelić, Dunja
AU  - Dubaić, Marija
AU  - Živković, Irena
AU  - Stević, Zorica
AU  - Giniatullin, Rashid
AU  - Andjus, Pavle
PY  - 2017
UR  - http://journal.frontiersin.org/article/10.3389/fimmu.2017.01619/full
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2928
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2–0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.
T2  - Frontiers in Immunology
T1  - Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line
IS  - NOV
VL  - 8
DO  - 10.3389/fimmu.2017.01619
SP  - 1619
ER  - 

@article{
author = "Milošević, Milena and Milićević, Katarina and Božić, Iva and Lavrnja, Irena and Stevanović, Ivana and Bijelić, Dunja and Dubaić, Marija and Živković, Irena and Stević, Zorica and Giniatullin, Rashid and Andjus, Pavle",
year = "2017",
abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2–0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.",
journal = "Frontiers in Immunology",
title = "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line",
number = "NOV",
volume = "8",
doi = "10.3389/fimmu.2017.01619",
pages = "1619"
}

Milošević, M., Milićević, K., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D., Dubaić, M., Živković, I., Stević, Z., Giniatullin, R.,& Andjus, P.. (2017). Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology, 8(NOV), 1619.
https://doi.org/10.3389/fimmu.2017.01619

Milošević M, Milićević K, Božić I, Lavrnja I, Stevanović I, Bijelić D, Dubaić M, Živković I, Stević Z, Giniatullin R, Andjus P. Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology. 2017;8(NOV):1619.
doi:10.3389/fimmu.2017.01619 .

Milošević, Milena, Milićević, Katarina, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja, Dubaić, Marija, Živković, Irena, Stević, Zorica, Giniatullin, Rashid, Andjus, Pavle, "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line" in Frontiers in Immunology, 8, no. NOV (2017):1619,
https://doi.org/10.3389/fimmu.2017.01619 . .

TY  - JOUR
AU  - Bataveljić, Danijela B.
AU  - Petrovic, Jelena
AU  - Lazic, Katarina
AU  - Šaponjić, Jasna
AU  - Andjus, Pavle
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2016
AB  - Alzheimer's disease (AD) involves selective loss of basal forebrain
   cholinergic neurons, particularly in the nucleus basalis (NB).
   Similarly, Parkinson's disease (PD) might involve the selective loss of
   pedunculopontine tegmental nucleus (PPT) cholinergic neurons. Therefore,
   lesions of these functionally distinct cholinergic centers in rats might
   serve as models of AD and PD cholinergic neuropathologies. Our previous
   articles described dissimilar sleep/wake-state disorders in rat models
   of AD and PD cholinergic neuropathologies. This study further examines
   astroglial and microglial responses as underlying pathologies in these
   distinct sleep disorders. Unilateral lesions of the NB or the PPT were
   induced with rats under ketamine/diazepam anesthesia (50 mg/kg i.p.) by
   using stereotaxically guided microinfusion of the excitotoxin ibotenic
   acid (IBO). Twenty-one days after the lesion, loss of cholinergic
   neurons was quantified by nicotinamide adenine dinucleotide
   phosphate-diaphorase histochemistry, and the astroglial and microglial
   responses were quantified by glia fibrillary acidic protein/OX42
   immunohistochemistry. This study demonstrates, for the first time, the
   anatomofunctionally related astroglial response following unilateral
   excitotoxic PPT cholinergic neuronal lesion. Whereas IBO NB and PPT
   lesions similarly enhanced local astroglial and microglial responses,
   astrogliosis in the PPT was followed by a remote astrogliosis within the
   ipslilateral NB. Conversely, there was no microglial response within the
   NB after PPT lesions. Our results reveal the rostrorostral PPT-NB
   astrogliosis after denervation of cholinergic neurons in the PPT. This
   hierarchically and anatomofunctionally guided PPT-NB astrogliosis
   emerged following cholinergic neuronal loss greater than 17\% throughout
   the overall rostrocaudal PPT dimension. (c) 2014 Wiley Periodicals, Inc.
T2  - Journal of Neuroscience Research
T1  - Glial Response in the Rat Models of Functionally Distinct Cholinergic
 Neuronal Denervations
IS  - 2
VL  - 93
DO  - 10.1002/jnr.23483
SP  - 244
EP  - 252
ER  - 

@article{
author = "Bataveljić, Danijela B. and Petrovic, Jelena and Lazic, Katarina and Šaponjić, Jasna and Andjus, Pavle",
year = "2015",
abstract = "Alzheimer's disease (AD) involves selective loss of basal forebrain
   cholinergic neurons, particularly in the nucleus basalis (NB).
   Similarly, Parkinson's disease (PD) might involve the selective loss of
   pedunculopontine tegmental nucleus (PPT) cholinergic neurons. Therefore,
   lesions of these functionally distinct cholinergic centers in rats might
   serve as models of AD and PD cholinergic neuropathologies. Our previous
   articles described dissimilar sleep/wake-state disorders in rat models
   of AD and PD cholinergic neuropathologies. This study further examines
   astroglial and microglial responses as underlying pathologies in these
   distinct sleep disorders. Unilateral lesions of the NB or the PPT were
   induced with rats under ketamine/diazepam anesthesia (50 mg/kg i.p.) by
   using stereotaxically guided microinfusion of the excitotoxin ibotenic
   acid (IBO). Twenty-one days after the lesion, loss of cholinergic
   neurons was quantified by nicotinamide adenine dinucleotide
   phosphate-diaphorase histochemistry, and the astroglial and microglial
   responses were quantified by glia fibrillary acidic protein/OX42
   immunohistochemistry. This study demonstrates, for the first time, the
   anatomofunctionally related astroglial response following unilateral
   excitotoxic PPT cholinergic neuronal lesion. Whereas IBO NB and PPT
   lesions similarly enhanced local astroglial and microglial responses,
   astrogliosis in the PPT was followed by a remote astrogliosis within the
   ipslilateral NB. Conversely, there was no microglial response within the
   NB after PPT lesions. Our results reveal the rostrorostral PPT-NB
   astrogliosis after denervation of cholinergic neurons in the PPT. This
   hierarchically and anatomofunctionally guided PPT-NB astrogliosis
   emerged following cholinergic neuronal loss greater than 17\% throughout
   the overall rostrocaudal PPT dimension. (c) 2014 Wiley Periodicals, Inc.",
journal = "Journal of Neuroscience Research",
title = "Glial Response in the Rat Models of Functionally Distinct Cholinergic
 Neuronal Denervations",
number = "2",
volume = "93",
doi = "10.1002/jnr.23483",
pages = "244-252"
}

Bataveljić, D. B., Petrovic, J., Lazic, K., Šaponjić, J.,& Andjus, P.. (2015). Glial Response in the Rat Models of Functionally Distinct Cholinergic
 Neuronal Denervations. in Journal of Neuroscience Research, 93(2), 244-252.
https://doi.org/10.1002/jnr.23483

Bataveljić DB, Petrovic J, Lazic K, Šaponjić J, Andjus P. Glial Response in the Rat Models of Functionally Distinct Cholinergic
 Neuronal Denervations. in Journal of Neuroscience Research. 2015;93(2):244-252.
doi:10.1002/jnr.23483 .

Bataveljić, Danijela B., Petrovic, Jelena, Lazic, Katarina, Šaponjić, Jasna, Andjus, Pavle, "Glial Response in the Rat Models of Functionally Distinct Cholinergic
 Neuronal Denervations" in Journal of Neuroscience Research, 93, no. 2 (2015):244-252,
https://doi.org/10.1002/jnr.23483 . .