TY  - CONF
AU  - Nikolic, Ljiljana
AU  - Bataveljic, Danijela
AU  - Bijelic, Dunja
AU  - Milicevic, Katarina
AU  - Bogdanović Pristov, Jelena
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2015
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  - Serbian Neuroscience Society, Belgrade
C3  - 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS
T1  - Background norepinephrine impacts activity of cortical astrocytes
SP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2015
ER  - 

@conference{
author = "Nikolic, Ljiljana and Bataveljic, Danijela and Bijelic, Dunja and Milicevic, 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 = "Serbian Neuroscience Society, Belgrade",
journal = "8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS",
title = "Background norepinephrine impacts activity of cortical astrocytes",
pages = "51",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2015"
}

Nikolic, L., Bataveljic, D., Bijelic, D., Milicevic, K.,& Bogdanović Pristov, J.. (2023). Background norepinephrine impacts activity of cortical astrocytes. in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS
Serbian Neuroscience Society, Belgrade., 51.
https://hdl.handle.net/21.15107/rcub_rimsi_2015

Nikolic L, Bataveljic D, Bijelic D, Milicevic K, Bogdanović Pristov J. Background norepinephrine impacts activity of cortical astrocytes. in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS. 2023;:51.
https://hdl.handle.net/21.15107/rcub_rimsi_2015 .

Nikolic, Ljiljana, Bataveljic, Danijela, Bijelic, Dunja, Milicevic, Katarina, Bogdanović Pristov, Jelena, "Background norepinephrine impacts activity of cortical astrocytes" in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS (2023):51,
https://hdl.handle.net/21.15107/rcub_rimsi_2015 .

TY  - CONF
AU  - Milicevic, Katarina
AU  - Bataveljic, Danijela
AU  - Bogdanović Pristov, Jelena
AU  - Andjus, Pavle
AU  - Nikolic, Ljiljana
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2009
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  P2X7receptor  (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 ofastrocyte purine-based interaction with immune cells.
PB  - Wiley Periodicals LLC
C3  - XVI European Meeting on Glial Cells in Health and Disease, Abstract booklet
T1  - P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells
SP  - E941
VL  - 71
DO  - https://doi.org/10.1002/glia.24419
ER  - 

@conference{
author = "Milicevic, Katarina and Bataveljic, Danijela and Bogdanović Pristov, Jelena and Andjus, Pavle and Nikolic, 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  P2X7receptor  (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 ofastrocyte purine-based interaction with immune cells.",
publisher = "Wiley Periodicals LLC",
journal = "XVI European Meeting on Glial Cells in Health and Disease, Abstract booklet",
title = "P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells",
pages = "E941",
volume = "71",
doi = "https://doi.org/10.1002/glia.24419"
}

Milicevic, K., Bataveljic, D., Bogdanović Pristov, J., Andjus, P.,& Nikolic, 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, Abstract booklet
Wiley Periodicals LLC., 71, E941.
https://doi.org/https://doi.org/10.1002/glia.24419

Milicevic K, Bataveljic D, Bogdanović Pristov J, Andjus P, Nikolic 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, Abstract booklet. 2023;71:E941.
doi:https://doi.org/10.1002/glia.24419 .

Milicevic, Katarina, Bataveljic, Danijela, Bogdanović Pristov, Jelena, Andjus, Pavle, Nikolic, 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, Abstract booklet, 71 (2023):E941,
https://doi.org/https://doi.org/10.1002/glia.24419 . .

TY  - CONF
AU  - Milicevic, Katarina
AU  - Bataveljic, Danijela
AU  - Bogdanović Pristov, Jelena
AU  - Andjus, Pavle
AU  - Nikolic, Ljiljana
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2014
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  - Serbian Neuroscience Society
C3  - 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS
T1  - αVβ3-Integrin and mitochondria mediate astrocyte response to  autoreactive immune cells
SP  - 101
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2014
ER  - 

@conference{
author = "Milicevic, Katarina and Bataveljic, Danijela and Bogdanović Pristov, Jelena and Andjus, Pavle and Nikolic, 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 = "Serbian Neuroscience Society",
journal = "8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS",
title = "αVβ3-Integrin and mitochondria mediate astrocyte response to  autoreactive immune cells",
pages = "101",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2014"
}

Milicevic, K., Bataveljic, D., Bogdanović Pristov, J., Andjus, P.,& Nikolic, L.. (2023). αVβ3-Integrin and mitochondria mediate astrocyte response to  autoreactive immune cells. in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS
Serbian Neuroscience Society., 101.
https://hdl.handle.net/21.15107/rcub_rimsi_2014

Milicevic K, Bataveljic D, Bogdanović Pristov J, Andjus P, Nikolic L. αVβ3-Integrin and mitochondria mediate astrocyte response to  autoreactive immune cells. in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS. 2023;:101.
https://hdl.handle.net/21.15107/rcub_rimsi_2014 .

Milicevic, Katarina, Bataveljic, Danijela, Bogdanović Pristov, Jelena, Andjus, Pavle, Nikolic, Ljiljana, "αVβ3-Integrin and mitochondria mediate astrocyte response to  autoreactive immune cells" in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS (2023):101,
https://hdl.handle.net/21.15107/rcub_rimsi_2014 .

TY  - JOUR
AU  - Milicevic, Katarina
AU  - Bataveljic, Danijela
AU  - Bogdanović Pristov, Jelena
AU  - Andjus, Pavle
AU  - Nikolic, Ljiljana
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2007
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
T2  - Cells
T1  - Astroglial Cell-to-Cell Interaction with Autoreactive Immune  Cells in Experimental Autoimmune Encephalomyelitis Involves  P2X7 Receptor, 3-Integrin, and Connexin-43
IS  - 13
SP  - 1786
VL  - 12
DO  - https://doi.org/10.3390/cells12131786
ER  - 

@article{
author = "Milicevic, Katarina and Bataveljic, Danijela and Bogdanović Pristov, Jelena and Andjus, Pavle and Nikolic, 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",
journal = "Cells",
title = "Astroglial Cell-to-Cell Interaction with Autoreactive Immune  Cells in Experimental Autoimmune Encephalomyelitis Involves  P2X7 Receptor, 3-Integrin, and Connexin-43",
number = "13",
pages = "1786",
volume = "12",
doi = "https://doi.org/10.3390/cells12131786"
}

Milicevic, K., Bataveljic, D., Bogdanović Pristov, J., Andjus, P.,& Nikolic, L.. (2023). Astroglial Cell-to-Cell Interaction with Autoreactive Immune  Cells in Experimental Autoimmune Encephalomyelitis Involves  P2X7 Receptor, 3-Integrin, and Connexin-43. in Cells
MDPI., 12(13), 1786.
https://doi.org/https://doi.org/10.3390/cells12131786

Milicevic K, Bataveljic D, Bogdanović Pristov J, Andjus P, Nikolic L. Astroglial Cell-to-Cell Interaction with Autoreactive Immune  Cells in Experimental Autoimmune Encephalomyelitis Involves  P2X7 Receptor, 3-Integrin, and Connexin-43. in Cells. 2023;12(13):1786.
doi:https://doi.org/10.3390/cells12131786 .

Milicevic, Katarina, Bataveljic, Danijela, Bogdanović Pristov, Jelena, Andjus, Pavle, Nikolic, Ljiljana, "Astroglial Cell-to-Cell Interaction with Autoreactive Immune  Cells in Experimental Autoimmune Encephalomyelitis Involves  P2X7 Receptor, 3-Integrin, and Connexin-43" in Cells, 12, no. 13 (2023):1786,
https://doi.org/https://doi.org/10.3390/cells12131786 . .

TY  - JOUR
AU  - Nobili, Paola
AU  - SHEN, Weida
AU  - Milicevic, Katarina
AU  - Bogdanović Pristov, Jelena
AU  - Audinat, Etienne
AU  - Nikolic, Ljiljana
PY  - 2022
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1813
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  - Frontiers Media
T2  - Frontiers in Pharmacology
T1  - Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis
SP  - 900337
VL  - 13
DO  - 10.3389/fphar.2022.900337
ER  - 

@article{
author = "Nobili, Paola and SHEN, Weida and Milicevic, Katarina and Bogdanović Pristov, Jelena and Audinat, Etienne and Nikolic, 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 = "Frontiers Media",
journal = "Frontiers in Pharmacology",
title = "Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis",
pages = "900337",
volume = "13",
doi = "10.3389/fphar.2022.900337"
}

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

Nobili P, SHEN W, Milicevic K, Bogdanović Pristov J, Audinat E, Nikolic 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, Milicevic, Katarina, Bogdanović Pristov, Jelena, Audinat, Etienne, Nikolic, 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  - CONF
AU  - Milicevic, Katarina
AU  - Bijelic, Dunja
AU  - Lazarevic, Milica
AU  - Miljkovic, Djordje
AU  - Bogdanović Pristov, Jelena
AU  - Petkovic, Branka
AU  - Andjus, Pavle
AU  - Momcilovic, Miljana
AU  - Nikolic, Ljiljana
PY  - 2020
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2017
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. Querétaro, México: Instituto de neurobiologia
T1  - Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes
SP  - 45
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2017
ER  - 

@conference{
author = "Milicevic, Katarina and Bijelic, Dunja and Lazarevic, Milica and Miljkovic, Djordje and Bogdanović Pristov, Jelena and Petkovic, Branka and Andjus, Pavle and Momcilovic, Miljana and Nikolic, 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. Querétaro, México: Instituto de neurobiologia",
title = "Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes",
pages = "45",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2017"
}

Milicevic, K., Bijelic, D., Lazarevic, M., Miljkovic, D., Bogdanović Pristov, J., Petkovic, B., Andjus, P., Momcilovic, M.,& Nikolic, 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
Querétaro, México: Instituto de neurobiologia., 45.
https://hdl.handle.net/21.15107/rcub_rimsi_2017

Milicevic K, Bijelic D, Lazarevic M, Miljkovic D, Bogdanović Pristov J, Petkovic B, Andjus P, Momcilovic M, Nikolic 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. Querétaro, México: Instituto de neurobiologia. 2020;:45.
https://hdl.handle.net/21.15107/rcub_rimsi_2017 .

Milicevic, Katarina, Bijelic, Dunja, Lazarevic, Milica, Miljkovic, Djordje, Bogdanović Pristov, Jelena, Petkovic, Branka, Andjus, Pavle, Momcilovic, Miljana, Nikolic, 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. Querétaro, México: Instituto de neurobiologia (2020):45,
https://hdl.handle.net/21.15107/rcub_rimsi_2017 .

TY  - CONF
AU  - Nikolic, Ljiljana
AU  - Bijelic, Dunja
AU  - Milicevic, Katarina
AU  - Momcilovic, Miljana
AU  - Bogdanović Pristov, Jelena
AU  - Petkovic, Branka
AU  - Andjus, Pavle
AU  - Miljkovic, Djordje
PY  - 2019
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2006
AB  - Aims: Multiple sclerosis (MS) is an in ammatory autoimmune disorder of the central nervous system (CNS). Complex interactions between inltrating 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  - Serbian Neuroscience Society, Belgrade
C3  - Federation of European Neuroscience Societies (FENS) Regional Meeting,Book of Abstract
T1  - ASTROCYTE ACTIVITY IN THE CENTRAL NERVOUS SYSTEM AUTOIMMUNITY
SP  - 295
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2006
ER  - 

@conference{
author = "Nikolic, Ljiljana and Bijelic, Dunja and Milicevic, Katarina and Momcilovic, Miljana and Bogdanović Pristov, Jelena and Petkovic, Branka and Andjus, Pavle and Miljkovic, Djordje",
year = "2019",
abstract = "Aims: Multiple sclerosis (MS) is an in ammatory autoimmune disorder of the central nervous system (CNS). Complex interactions between inltrating 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 = "Serbian Neuroscience Society, Belgrade",
journal = "Federation of European Neuroscience Societies (FENS) Regional Meeting,Book of Abstract",
title = "ASTROCYTE ACTIVITY IN THE CENTRAL NERVOUS SYSTEM AUTOIMMUNITY",
pages = "295",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2006"
}

Nikolic, L., Bijelic, D., Milicevic, K., Momcilovic, M., Bogdanović Pristov, J., Petkovic, B., Andjus, P.,& Miljkovic, D.. (2019). ASTROCYTE ACTIVITY IN THE CENTRAL NERVOUS SYSTEM AUTOIMMUNITY. in Federation of European Neuroscience Societies (FENS) Regional Meeting,Book of Abstract
Serbian Neuroscience Society, Belgrade., 295.
https://hdl.handle.net/21.15107/rcub_rimsi_2006

Nikolic L, Bijelic D, Milicevic K, Momcilovic M, Bogdanović Pristov J, Petkovic B, Andjus P, Miljkovic D. ASTROCYTE ACTIVITY IN THE CENTRAL NERVOUS SYSTEM AUTOIMMUNITY. in Federation of European Neuroscience Societies (FENS) Regional Meeting,Book of Abstract. 2019;:295.
https://hdl.handle.net/21.15107/rcub_rimsi_2006 .

Nikolic, Ljiljana, Bijelic, Dunja, Milicevic, Katarina, Momcilovic, Miljana, Bogdanović Pristov, Jelena, Petkovic, Branka, Andjus, Pavle, Miljkovic, Djordje, "ASTROCYTE ACTIVITY IN THE CENTRAL NERVOUS SYSTEM AUTOIMMUNITY" in Federation of European Neuroscience Societies (FENS) Regional Meeting,Book of Abstract (2019):295,
https://hdl.handle.net/21.15107/rcub_rimsi_2006 .