Nikolic, Ljiljana

Link to this page

Authority KeyName Variants
d900145d-1233-4e08-8f12-cabeb90bc356
  • Nikolic, Ljiljana (14)
Projects

Author's Bibliography

GnRHR signaling in neuronal cells: in vitro and in vivo data

Milosevic, Ana; Milosevic, Katarina; Nikolic, Ljiljana; Bogdanović Pristov, Jelena; Božić, Iva; Zivkovic, Anica; Lavrnja, Irena; Savic, Danijela; Janjic, Marija; Bjelobaba, Ivana

(Belgrade: Serbian Neuroscience Society, 2023)

TY  - CONF
AU  - Milosevic, Ana
AU  - Milosevic, Katarina
AU  - Nikolic, Ljiljana
AU  - Bogdanović Pristov, Jelena
AU  - Božić, Iva
AU  - Zivkovic, Anica
AU  - Lavrnja, Irena
AU  - Savic, Danijela
AU  - Janjic, Marija
AU  - Bjelobaba, Ivana
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2019
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  - 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS
T1  - GnRHR signaling in neuronal cells: in vitro and in vivo data
SP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2019
ER  - 
@conference{
author = "Milosevic, Ana and Milosevic, Katarina and Nikolic, Ljiljana and Bogdanović Pristov, Jelena and Božić, Iva and Zivkovic, Anica and Lavrnja, Irena and Savic, Danijela and Janjic, 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 = "8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS",
title = "GnRHR signaling in neuronal cells: in vitro and in vivo data",
pages = "53",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2019"
}
Milosevic, A., Milosevic, K., Nikolic, L., Bogdanović Pristov, J., Božić, I., Zivkovic, A., Lavrnja, I., Savic, D., Janjic, M.,& Bjelobaba, I.. (2023). GnRHR signaling in neuronal cells: in vitro and in vivo data. in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS
Belgrade: Serbian Neuroscience Society., 53.
https://hdl.handle.net/21.15107/rcub_rimsi_2019
Milosevic A, Milosevic K, Nikolic L, Bogdanović Pristov J, Božić I, Zivkovic A, Lavrnja I, Savic D, Janjic M, Bjelobaba I. GnRHR signaling in neuronal cells: in vitro and in vivo data. in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS. 2023;:53.
https://hdl.handle.net/21.15107/rcub_rimsi_2019 .
Milosevic, Ana, Milosevic, Katarina, Nikolic, Ljiljana, Bogdanović Pristov, Jelena, Božić, Iva, Zivkovic, Anica, Lavrnja, Irena, Savic, Danijela, Janjic, Marija, Bjelobaba, Ivana, "GnRHR signaling in neuronal cells: in vitro and in vivo data" in 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international  participation  31 May – 2 June 2023. Belgrade, Serbia - BOOK OF ABSTRACTS (2023):53,
https://hdl.handle.net/21.15107/rcub_rimsi_2019 .

Background norepinephrine impacts activity of cortical astrocytes

Nikolic, Ljiljana; Bataveljic, Danijela; Bijelic, Dunja; Milicevic, Katarina; Bogdanović Pristov, Jelena

(Serbian Neuroscience Society, Belgrade, 2023)

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 .

P2X7R, β3-integrin and Cx-43 mediate interaction between astrocytes and adjacent autoreactive immune cells

Milicevic, Katarina; Bataveljic, Danijela; Bogdanović Pristov, Jelena; Andjus, Pavle; Nikolic, Ljiljana

(Wiley Periodicals LLC, 2023)

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 . .

αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells

Milicevic, Katarina; Bataveljic, Danijela; Bogdanović Pristov, Jelena; Andjus, Pavle; Nikolic, Ljiljana

(Serbian Neuroscience Society, 2023)

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 .

Astroglial Cell-to-Cell Interaction with Autoreactive Immune Cells in Experimental Autoimmune Encephalomyelitis Involves P2X7 Receptor, 3-Integrin, and Connexin-43

Milicevic, Katarina; Bataveljic, Danijela; Bogdanović Pristov, Jelena; Andjus, Pavle; Nikolic, Ljiljana

(MDPI, 2023)

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 . .

Can glial cells save neurons in epilepsy?

SHEN, Weida; Bogdanović Pristov, Jelena; Nobili, Paola; Nikolic, Ljiljana

(Wolters Kluwer – Medknow, 2023)

TY  - JOUR
AU  - SHEN, Weida
AU  - Bogdanović Pristov, Jelena
AU  - Nobili, Paola
AU  - Nikolic, Ljiljana
PY  - 2023
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2004
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.
PB  - Wolters Kluwer – Medknow
T2  - NEURAL REGENERATION RESEARCH
T1  - Can glial cells save neurons in epilepsy?
EP  - 1422
IS  - 7
SP  - 1417
VL  - 18
DO  - 10.4103/1673-5374.360281
ER  - 
@article{
author = "SHEN, Weida and Bogdanović Pristov, Jelena and Nobili, Paola and Nikolic, 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.",
publisher = "Wolters Kluwer – Medknow",
journal = "NEURAL REGENERATION RESEARCH",
title = "Can glial cells save neurons in epilepsy?",
pages = "1422-1417",
number = "7",
volume = "18",
doi = "10.4103/1673-5374.360281"
}
SHEN, W., Bogdanović Pristov, J., Nobili, P.,& Nikolic, L.. (2023). Can glial cells save neurons in epilepsy?. in NEURAL REGENERATION RESEARCH
Wolters Kluwer – Medknow., 18(7), 1417-1422.
https://doi.org/10.4103/1673-5374.360281
SHEN W, Bogdanović Pristov J, Nobili P, Nikolic 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, Nikolic, 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 . .
7

MEMBRANE CURRENTS OF C6 CELLS IN PHARMACOLOGICAL INVESTIGATION

Nikolic, Ljiljana; Savic, Danijela; Korać Jačić, Jelena; Petkovic, Branka; Stojadinovic, Gordana; Martac, Ljiljana; Bogdanović Pristov, Jelena

(Society of Physical Chemists of Serbia, 2022)

TY  - CONF
AU  - Nikolic, Ljiljana
AU  - Savic, Danijela
AU  - Korać Jačić, Jelena
AU  - Petkovic, Branka
AU  - Stojadinovic, Gordana
AU  - Martac, Ljiljana
AU  - Bogdanović Pristov, Jelena
PY  - 2022
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2010
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  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings)
T1  - MEMBRANE CURRENTS OF C6 CELLS IN PHARMACOLOGICAL  INVESTIGATION
EP  - 592
SP  - 589
VL  - 2
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2010
ER  - 
@conference{
author = "Nikolic, Ljiljana and Savic, Danijela and Korać Jačić, Jelena and Petkovic, Branka and Stojadinovic, Gordana and Martac, 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 = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings)",
title = "MEMBRANE CURRENTS OF C6 CELLS IN PHARMACOLOGICAL  INVESTIGATION",
pages = "592-589",
volume = "2",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2010"
}
Nikolic, L., Savic, D., Korać Jačić, J., Petkovic, B., Stojadinovic, G., Martac, L.,& Bogdanović Pristov, J.. (2022). MEMBRANE CURRENTS OF C6 CELLS IN PHARMACOLOGICAL  INVESTIGATION. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings)
Society of Physical Chemists of Serbia., 2, 589-592.
https://hdl.handle.net/21.15107/rcub_rimsi_2010
Nikolic L, Savic D, Korać Jačić J, Petkovic B, Stojadinovic G, Martac L, Bogdanović Pristov J. MEMBRANE CURRENTS OF C6 CELLS IN PHARMACOLOGICAL  INVESTIGATION. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings). 2022;2:589-592.
https://hdl.handle.net/21.15107/rcub_rimsi_2010 .
Nikolic, Ljiljana, Savic, Danijela, Korać Jačić, Jelena, Petkovic, Branka, Stojadinovic, Gordana, Martac, Ljiljana, Bogdanović Pristov, Jelena, "MEMBRANE CURRENTS OF C6 CELLS IN PHARMACOLOGICAL  INVESTIGATION" in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings), 2 (2022):589-592,
https://hdl.handle.net/21.15107/rcub_rimsi_2010 .

PROTOPLAST PATCH-CLAMPING USING AN UPRIGHT MICROSCOPE WITH A MOVABLE STAGE

Nikolic, Ljiljana; Vidović, Marija; Todorovic, Natasa; Petkovic, Branka; Stojadinovic, Gordana; Martac, Ljiljana; Bogdanović Pristov, Jelena

(Society of Physical Chemists of Serbia, 2022)

TY  - CONF
AU  - Nikolic, Ljiljana
AU  - Vidović, Marija
AU  - Todorovic, Natasa
AU  - Petkovic, Branka
AU  - Stojadinovic, Gordana
AU  - Martac, Ljiljana
AU  - Bogdanović Pristov, Jelena
PY  - 2022
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2008
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 patch
clamp. 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 patch clamping, can be applied to study membrane properties of root protoplasts.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings)
T1  - PROTOPLAST PATCH-CLAMPING USING AN UPRIGHT MICROSCOPE  WITH A MOVABLE STAGE
EP  - 274
SP  - 271
VL  - 1
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2008
ER  - 
@conference{
author = "Nikolic, Ljiljana and Vidović, Marija and Todorovic, Natasa and Petkovic, Branka and Stojadinovic, Gordana and Martac, 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 patch
clamp. 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 patch clamping, can be applied to study membrane properties of root protoplasts.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings)",
title = "PROTOPLAST PATCH-CLAMPING USING AN UPRIGHT MICROSCOPE  WITH A MOVABLE STAGE",
pages = "274-271",
volume = "1",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2008"
}
Nikolic, L., Vidović, M., Todorovic, N., Petkovic, B., Stojadinovic, G., Martac, L.,& Bogdanović Pristov, J.. (2022). PROTOPLAST PATCH-CLAMPING USING AN UPRIGHT MICROSCOPE  WITH A MOVABLE STAGE. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings)
Society of Physical Chemists of Serbia., 1, 271-274.
https://hdl.handle.net/21.15107/rcub_rimsi_2008
Nikolic L, Vidović M, Todorovic N, Petkovic B, Stojadinovic G, Martac L, Bogdanović Pristov J. PROTOPLAST PATCH-CLAMPING USING AN UPRIGHT MICROSCOPE  WITH A MOVABLE STAGE. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings). 2022;1:271-274.
https://hdl.handle.net/21.15107/rcub_rimsi_2008 .
Nikolic, Ljiljana, Vidović, Marija, Todorovic, Natasa, Petkovic, Branka, Stojadinovic, Gordana, Martac, Ljiljana, Bogdanović Pristov, Jelena, "PROTOPLAST PATCH-CLAMPING USING AN UPRIGHT MICROSCOPE  WITH A MOVABLE STAGE" in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects  of Physical Chemistry (Proceedings), 1 (2022):271-274,
https://hdl.handle.net/21.15107/rcub_rimsi_2008 .

Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis

Nobili, Paola; SHEN, Weida; Milicevic, Katarina; Bogdanović Pristov, Jelena; Audinat, Etienne; Nikolic, Ljiljana

(Frontiers Media, 2022)

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 . .
1
8

Central nervous system-infiltrated immune cells alter calcium dynamics in astrocytes

Milicevic, Katarina; Bijelic, Dunja; Lazarevic, Milica; Miljkovic, Djordje; Bogdanović Pristov, Jelena; Petkovic, Branka; Andjus, Pavle; Momcilovic, Miljana; Nikolic, Ljiljana

(Querétaro, México: Instituto de neurobiologia, 2020)

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 .

Iron modulates norepinephrine effect on astrocytes

Nikolic, Ljiljana; Korać Jačić, Jelena; Bijelic, Dunja; Spasojević, Ivan; Bogdanović Pristov, Jelena

(COST Action CA15133, 2019)

TY  - CONF
AU  - Nikolic, Ljiljana
AU  - Korać Jačić, Jelena
AU  - Bijelic, Dunja
AU  - Spasojević, Ivan
AU  - Bogdanović Pristov, Jelena
PY  - 2019
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2020
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_rimsi_2020
ER  - 
@conference{
author = "Nikolic, Ljiljana and Korać Jačić, Jelena and Bijelic, 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_rimsi_2020"
}
Nikolic, L., Korać Jačić, J., Bijelic, 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_rimsi_2020
Nikolic L, Korać Jačić J, Bijelic 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_rimsi_2020 .
Nikolic, Ljiljana, Korać Jačić, Jelena, Bijelic, 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_rimsi_2020 .

IRON MODULATES NOREPINEPHRINE EFFECT ON ASTROCYTES

Korać Jačić, Jelena; Nikolic, Ljiljana; Bijelic, Dunja; Spasojević, Ivan; Bogdanović Pristov, Jelena

(Serbian Neuroscience Society, Belgrade, 2019)

TY  - CONF
AU  - Korać Jačić, Jelena
AU  - Nikolic, Ljiljana
AU  - Bijelic, Dunja
AU  - Spasojević, Ivan
AU  - Bogdanović Pristov, Jelena
PY  - 2019
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2016
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 modified by iron.
PB  - Serbian Neuroscience Society, Belgrade
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_rimsi_2016
ER  - 
@conference{
author = "Korać Jačić, Jelena and Nikolic, Ljiljana and Bijelic, 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 modified by iron.",
publisher = "Serbian Neuroscience Society, Belgrade",
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_rimsi_2016"
}
Korać Jačić, J., Nikolic, L., Bijelic, 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.
Serbian Neuroscience Society, Belgrade., 370.
https://hdl.handle.net/21.15107/rcub_rimsi_2016
Korać Jačić J, Nikolic L, Bijelic 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_rimsi_2016 .
Korać Jačić, Jelena, Nikolic, Ljiljana, Bijelic, 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_rimsi_2016 .

ASTROCYTE ACTIVITY IN THE CENTRAL NERVOUS SYSTEM AUTOIMMUNITY

Nikolic, Ljiljana; Bijelic, Dunja; Milicevic, Katarina; Momcilovic, Miljana; Bogdanović Pristov, Jelena; Petkovic, Branka; Andjus, Pavle; Miljkovic, Djordje

(Serbian Neuroscience Society, Belgrade, 2019)

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 .

Redox interactions of epinephrine with iron at physiological pH

Korać Jačić, Jelena; Stanković, Dalibor; Bogdanović Pristov, Jelena; Nikolic, Ljiljana; Spasojević, Ivan

(Biohemijsko drustvo Srbije, 2018)

TY  - CONF
AU  - Korać Jačić, Jelena
AU  - Stanković, Dalibor
AU  - Bogdanović Pristov, Jelena
AU  - Nikolic, Ljiljana
AU  - Spasojević, Ivan
PY  - 2018
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2844
AB  - Epinephrine ((R)-4-(1-hydroxy-2-(methylamino)ethyl)-benzene-1,2-diol (Epi) is catecholamine that is released by the sympathetic nervous system and adrenal medulla. It is a physiologically important molecule that acts as a hormone, neurotransmitter, and medication with a broad range of effects 1-3 . Coordinate and redox interaction of Epi with iron affects the interactions with other molecules and its biological effects 4 . In this study, we reported details of redox interactions of Epi with Fe 2+ at pH 7.4, which correspond to the pH value of human plasma Epi and Fe 2+ form a complex that acts as a strong reducing agent. Cyclic voltammetry showed that the positions of E pa and E pc potentials were at approximately -480 and -1100 mV. This implies that Epi and Fe 2+ build a complex with unique redox properties. E1/2 was significantly lower compared to E0' for O 2 /O 2•- (-350 mV). It is important to point out this because superoxide radical anion is produced via spontaneous Fe 2+ reaction with O 2. In other words, Epi-Fe 2+ complex should be capable of reducing transition metals in (patho)physiologicaly relevant complexes that are not susceptible to reduction by O 2. Our results confirmed that Epi-Fe 2+ is capable of reducing the S-S group of glutathione disulfide. On the other hand, Epi acted in a catalyst-like fashion to promote Fe 2+ oxidation by molecular oxygen, and to a facilitated formation of the Epi–Fe 3+ complexes, at physiological pH. In addition, we examined the effects of epinepfrine and Epi/Fe3+ system on glioma cells. Epinephrine alone evokes changes in the membrane currents of glioma cells, but such effects were not observed for the complex with Fe 3+ . This implies that Epi-Fe 3+ might modulate neural activity of Epi in CNS.
PB  - Biohemijsko drustvo Srbije
C3  - Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia
T1  - Redox interactions of epinephrine with iron at physiological pH
EP  - 142
SP  - 141
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2844
ER  - 
@conference{
author = "Korać Jačić, Jelena and Stanković, Dalibor and Bogdanović Pristov, Jelena and Nikolic, Ljiljana and Spasojević, Ivan",
year = "2018",
abstract = "Epinephrine ((R)-4-(1-hydroxy-2-(methylamino)ethyl)-benzene-1,2-diol (Epi) is catecholamine that is released by the sympathetic nervous system and adrenal medulla. It is a physiologically important molecule that acts as a hormone, neurotransmitter, and medication with a broad range of effects 1-3 . Coordinate and redox interaction of Epi with iron affects the interactions with other molecules and its biological effects 4 . In this study, we reported details of redox interactions of Epi with Fe 2+ at pH 7.4, which correspond to the pH value of human plasma Epi and Fe 2+ form a complex that acts as a strong reducing agent. Cyclic voltammetry showed that the positions of E pa and E pc potentials were at approximately -480 and -1100 mV. This implies that Epi and Fe 2+ build a complex with unique redox properties. E1/2 was significantly lower compared to E0' for O 2 /O 2•- (-350 mV). It is important to point out this because superoxide radical anion is produced via spontaneous Fe 2+ reaction with O 2. In other words, Epi-Fe 2+ complex should be capable of reducing transition metals in (patho)physiologicaly relevant complexes that are not susceptible to reduction by O 2. Our results confirmed that Epi-Fe 2+ is capable of reducing the S-S group of glutathione disulfide. On the other hand, Epi acted in a catalyst-like fashion to promote Fe 2+ oxidation by molecular oxygen, and to a facilitated formation of the Epi–Fe 3+ complexes, at physiological pH. In addition, we examined the effects of epinepfrine and Epi/Fe3+ system on glioma cells. Epinephrine alone evokes changes in the membrane currents of glioma cells, but such effects were not observed for the complex with Fe 3+ . This implies that Epi-Fe 3+ might modulate neural activity of Epi in CNS.",
publisher = "Biohemijsko drustvo Srbije",
journal = "Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia",
title = "Redox interactions of epinephrine with iron at physiological pH",
pages = "142-141",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2844"
}
Korać Jačić, J., Stanković, D., Bogdanović Pristov, J., Nikolic, L.,& Spasojević, I.. (2018). Redox interactions of epinephrine with iron at physiological pH. in Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia
Biohemijsko drustvo Srbije., 141-142.
https://hdl.handle.net/21.15107/rcub_rimsi_2844
Korać Jačić J, Stanković D, Bogdanović Pristov J, Nikolic L, Spasojević I. Redox interactions of epinephrine with iron at physiological pH. in Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia. 2018;:141-142.
https://hdl.handle.net/21.15107/rcub_rimsi_2844 .
Korać Jačić, Jelena, Stanković, Dalibor, Bogdanović Pristov, Jelena, Nikolic, Ljiljana, Spasojević, Ivan, "Redox interactions of epinephrine with iron at physiological pH" in Proceedings: Serbian Biochemical Society Eigth Conference with international participation: Coordination in Biochemistry and Life; 2018 Nov 16; Novi Sad, Serbia (2018):141-142,
https://hdl.handle.net/21.15107/rcub_rimsi_2844 .