Milićević, Katarina

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  • Milićević, Katarina (9)

Author's Bibliography

Background norepinephrine impacts activity of cortical astrocytes

Nikolić, Ljiljana; Bataveljić, Danijela; Bijelić, Dunja; Milićević, Katarina; Bogdanović Pristov, Jelena

(Belgrade: Serbian Neuroscience Society, 2023)

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

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

cortical astrocytes to bypass NE targeting of multiple cell types.
We show that cortical astrocytes detect and respond to the background NE
concentration with an increase in intracellular Ca2+. This Ca2+ liberated from
intracellular stores further increased large-conductance, Ca2+-sensitive potassium
(BK) currents in astrocytes. Notably, immunohistochemistry data showed that BK
channels and alpha 1 adrenoreceptor are highly expressed in astrocytes in the rat
cortex. Furthermore, stimulation of astrocytes by background NE was inhibited by
alpha-adrenoceptor antagonist.
Our results suggest that astrocytes maintain basal brain activity by perceiving and
responding to the background NE.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Background norepinephrine impacts activity of cortical astrocytes
SP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5835
ER  - 
@conference{
author = "Nikolić, Ljiljana and Bataveljić, Danijela and Bijelić, Dunja and Milićević, Katarina and Bogdanović Pristov, Jelena",
year = "2023",
abstract = "The neurotransmitter norepinephrine (NE) plays a central role in regulating arousal,
attention, cognitive function and stress responses. Unlike fast neurotransmitters which
act at synapses, NE is released in the neuropil and performs multiple targeting in the
surrounding area. The glial cells astrocytes are a direct target of NE, as they express
all adrenergic receptor subtypes and respond with Ca2+ increases to NE. Astroglial
responses elicited by strong and transient increases of NE in the brain are well studied,
but the effect of a low background NE concentration on astrocytes is unknown. This
background level of NE is maintained by basal noradrenergic activity and is
constantly present in the brain. Therefore, the response of astrocytes to the
background NE could have been unintentionally evoked in previous studies but its
effect overlooked.

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

cortical astrocytes to bypass NE targeting of multiple cell types.
We show that cortical astrocytes detect and respond to the background NE
concentration with an increase in intracellular Ca2+. This Ca2+ liberated from
intracellular stores further increased large-conductance, Ca2+-sensitive potassium
(BK) currents in astrocytes. Notably, immunohistochemistry data showed that BK
channels and alpha 1 adrenoreceptor are highly expressed in astrocytes in the rat
cortex. Furthermore, stimulation of astrocytes by background NE was inhibited by
alpha-adrenoceptor antagonist.
Our results suggest that astrocytes maintain basal brain activity by perceiving and
responding to the background NE.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Background norepinephrine impacts activity of cortical astrocytes",
pages = "51",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5835"
}
Nikolić, L., Bataveljić, D., Bijelić, D., Milićević, K.,& Bogdanović Pristov, J.. (2023). Background norepinephrine impacts activity of cortical astrocytes. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 51.
https://hdl.handle.net/21.15107/rcub_ibiss_5835
Nikolić L, Bataveljić D, Bijelić D, Milićević K, Bogdanović Pristov J. Background norepinephrine impacts activity of cortical astrocytes. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:51.
https://hdl.handle.net/21.15107/rcub_ibiss_5835 .
Nikolić, Ljiljana, Bataveljić, Danijela, Bijelić, Dunja, Milićević, Katarina, Bogdanović Pristov, Jelena, "Background norepinephrine impacts activity of cortical astrocytes" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):51,
https://hdl.handle.net/21.15107/rcub_ibiss_5835 .

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

Milićević, Katarina; Bataveljić, Danijela; Bogdanović Pristov, Jelena; Anđus, Pavle; Nikolić, Ljiljana

(Belgrade: Serbian Neuroscience Society, 2023)

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

/Ca2+- exchangers in astrocytes promoted an augmentation of the
intracellular Ca2+ increase and a higher ATP release after brief exposure to CNS-IICs,
demonstrating that mitochondria regulate the astrocyte-CNS IICs cell-cell interaction.
Overall, our study expands the understanding of astrocytes’ interaction with
autoreactive immune cells that are present in their local environment in an
autoimmune disease. This offers a new conceptual framework for considering direct
astrocyte–immune cell interaction to design new strategies for therapy development in
the treatment of MS.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells
SP  - 101
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5837
ER  - 
@conference{
author = "Milićević, Katarina and Bataveljić, Danijela and Bogdanović Pristov, Jelena and Anđus, Pavle and Nikolić, Ljiljana",
year = "2023",
abstract = "The astrocytic network maintains homeostasis in the central nervous system (CNS)
through interactions with neighboring cells. In the CNS autoimmune disease, multiple
sclerosis (MS), neuroinflammatory conditions modulate these cell-to-cell interactions.
Our previous work revealed that the immune cells infiltrated into the CNS (CNS-IICs)
of experimental autoimmune encemphalomyelitis (EAE) rat, an animal model of MS,
rapidly alter the activity pattern of astrocytes by activating the glial P2X7 receptor
(P2X7R). In the present study we further defined the mechanisms responsible for
astrocytes’ activation in the presence of CNS-IICs. For this purpose, we used an in
vitro experimental setup and monitored Ca2+ dynamics in Fluo-4-labeled cultured
naïve astrocytes following brief bath application of CNS-IICs isolated from the spinal
cord of the EAE rat. Our data indicate that the astroglial αvβ3-integrin is involved in
the initial contact of astrocytes with CNS-IICs, since blocking αvβ3-integrin reduced
the expected astrocytic Ca2+ response. Furthermore, blocking of mitochondrial
Na+
/Ca2+- and H+

/Ca2+- exchangers in astrocytes promoted an augmentation of the
intracellular Ca2+ increase and a higher ATP release after brief exposure to CNS-IICs,
demonstrating that mitochondria regulate the astrocyte-CNS IICs cell-cell interaction.
Overall, our study expands the understanding of astrocytes’ interaction with
autoreactive immune cells that are present in their local environment in an
autoimmune disease. This offers a new conceptual framework for considering direct
astrocyte–immune cell interaction to design new strategies for therapy development in
the treatment of MS.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells",
pages = "101",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5837"
}
Milićević, K., Bataveljić, D., Bogdanović Pristov, J., Anđus, P.,& Nikolić, L.. (2023). αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 101.
https://hdl.handle.net/21.15107/rcub_ibiss_5837
Milićević K, Bataveljić D, Bogdanović Pristov J, Anđus P, Nikolić L. αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:101.
https://hdl.handle.net/21.15107/rcub_ibiss_5837 .
Milićević, Katarina, Bataveljić, Danijela, Bogdanović Pristov, Jelena, Anđus, Pavle, Nikolić, Ljiljana, "αVβ3-Integrin and mitochondria mediate astrocyte response to autoreactive immune cells" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):101,
https://hdl.handle.net/21.15107/rcub_ibiss_5837 .

Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.

Nobili, Paola; Shen, Weida; Milićević, Katarina; Bogdanović Pristov, Jelena; Audinat, Etienne; Nikolić, Ljiljana

(Lausanne: Frontiers Media S.A., 2022)

TY  - JOUR
AU  - Nobili, Paola
AU  - Shen, Weida
AU  - Milićević, Katarina
AU  - Bogdanović Pristov, Jelena
AU  - Audinat, Etienne
AU  - Nikolić, Ljiljana
PY  - 2022
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2022.900337/full
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4989
AB  - Epilepsy and multiple sclerosis (MS), two of the most common neurological diseases, are characterized by the establishment of inflammatory environment in the central nervous system that drives disease progression and impacts on neurodegeneration. Current therapeutic approaches in the treatments of epilepsy and MS are targeting neuronal activity and immune cell response, respectively. However, the lack of fully efficient responses to the available treatments obviously shows the need to search for novel therapeutic candidates that will not exclusively target neurons or immune cells. Accumulating knowledge on epilepsy and MS in humans and analysis of relevant animal models, reveals that astrocytes are promising therapeutic candidates to target as they participate in the modulation of the neuroinflammatory response in both diseases from the initial stages and may play an important role in their development. Indeed, astrocytes respond to reactive immune cells and contribute to the neuronal hyperactivity in the inflamed brain. Mechanistically, these astrocytic cell to cell interactions are fundamentally mediated by the purinergic signalling and involve metabotropic P2Y1 receptors in case of astrocyte interactions with neurons, while ionotropic P2X7 receptors are mainly involved in astrocyte interactions with autoreactive immune cells. Herein, we review the potential of targeting astrocytic purinergic signalling mediated by P2Y1 and P2X7 receptors to develop novel approaches for treatments of epilepsy and MS at very early stages.
PB  - Lausanne: Frontiers Media S.A.
T2  - Frontiers in Pharmacology
T1  - Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.
VL  - 13
DO  - 10.3389/fphar.2022.900337
SP  - 900337
ER  - 
@article{
author = "Nobili, Paola and Shen, Weida and Milićević, Katarina and Bogdanović Pristov, Jelena and Audinat, Etienne and Nikolić, Ljiljana",
year = "2022",
abstract = "Epilepsy and multiple sclerosis (MS), two of the most common neurological diseases, are characterized by the establishment of inflammatory environment in the central nervous system that drives disease progression and impacts on neurodegeneration. Current therapeutic approaches in the treatments of epilepsy and MS are targeting neuronal activity and immune cell response, respectively. However, the lack of fully efficient responses to the available treatments obviously shows the need to search for novel therapeutic candidates that will not exclusively target neurons or immune cells. Accumulating knowledge on epilepsy and MS in humans and analysis of relevant animal models, reveals that astrocytes are promising therapeutic candidates to target as they participate in the modulation of the neuroinflammatory response in both diseases from the initial stages and may play an important role in their development. Indeed, astrocytes respond to reactive immune cells and contribute to the neuronal hyperactivity in the inflamed brain. Mechanistically, these astrocytic cell to cell interactions are fundamentally mediated by the purinergic signalling and involve metabotropic P2Y1 receptors in case of astrocyte interactions with neurons, while ionotropic P2X7 receptors are mainly involved in astrocyte interactions with autoreactive immune cells. Herein, we review the potential of targeting astrocytic purinergic signalling mediated by P2Y1 and P2X7 receptors to develop novel approaches for treatments of epilepsy and MS at very early stages.",
publisher = "Lausanne: Frontiers Media S.A.",
journal = "Frontiers in Pharmacology",
title = "Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.",
volume = "13",
doi = "10.3389/fphar.2022.900337",
pages = "900337"
}
Nobili, P., Shen, W., Milićević, K., Bogdanović Pristov, J., Audinat, E.,& Nikolić, L.. (2022). Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.. in Frontiers in Pharmacology
Lausanne: Frontiers Media S.A.., 13, 900337.
https://doi.org/10.3389/fphar.2022.900337
Nobili P, Shen W, Milićević K, Bogdanović Pristov J, Audinat E, Nikolić L. Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis.. in Frontiers in Pharmacology. 2022;13:900337.
doi:10.3389/fphar.2022.900337 .
Nobili, Paola, Shen, Weida, Milićević, Katarina, Bogdanović Pristov, Jelena, Audinat, Etienne, Nikolić, Ljiljana, "Therapeutic Potential of Astrocyte Purinergic Signalling in Epilepsy and Multiple Sclerosis." in Frontiers in Pharmacology, 13 (2022):900337,
https://doi.org/10.3389/fphar.2022.900337 . .
1
8

Approach for patch-clamping using an upright microscope with z-axis movable stage.

Perić, Mina; Bataveljić, Danijela; Bijelić, Dunja; Milićević, Katarina; Andjus, Pavle R.; Bogdanović Pristov, Jelena; Nikolić, Ljiljana

(Hoboken: John Wiley and Sons Inc., 2022)

TY  - JOUR
AU  - Perić, Mina
AU  - Bataveljić, Danijela
AU  - Bijelić, Dunja
AU  - Milićević, Katarina
AU  - Andjus, Pavle R.
AU  - Bogdanović Pristov, Jelena
AU  - Nikolić, Ljiljana
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/jemt.24066
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35088507
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4790
AB  - We describe an approach for studying the physiology of single live cells using the conceptionally novel upright microscope/patch-clamp configuration. Electrophysiology experiments typically require a microscope with the fixed stage position and the motion control of the microscope objective. Here, we demonstrate that a microscope with a z-axis movable stage and a fixed objective can also be efficiently used in combination with the patch-clamp technique. We define a set of underlying principles governing the operation of this microscope/patch-clamp configuration and demonstrate its performance in practice using cultured astrocytes, microglia, and oligodendrocytes. Experimental results show that our custom configuration provides stable recordings, has a high success rate of the whole-cell patch-clamp trials, can be effectively applied to study cellular physiology of glial cells, and provides comparable performance and usability to the commercially available systems. Our system can be easily replicated or adapted to suit the needs of the research groups and can be cost-effective in reducing the investments in purchasing additional equipment. We provide step-by-step instructions on implementing an upright microscope with z-axis movable stage as a routine workhorse for patch-clamping.
PB  - Hoboken: John Wiley and Sons Inc.
T2  - Microscopy Research and Technique
T1  - Approach for patch-clamping using an upright microscope with z-axis movable stage.
IS  - 6
VL  - 85
DO  - 10.1002/jemt.24066
SP  - 2095
EP  - 2104
ER  - 
@article{
author = "Perić, Mina and Bataveljić, Danijela and Bijelić, Dunja and Milićević, Katarina and Andjus, Pavle R. and Bogdanović Pristov, Jelena and Nikolić, Ljiljana",
year = "2022",
abstract = "We describe an approach for studying the physiology of single live cells using the conceptionally novel upright microscope/patch-clamp configuration. Electrophysiology experiments typically require a microscope with the fixed stage position and the motion control of the microscope objective. Here, we demonstrate that a microscope with a z-axis movable stage and a fixed objective can also be efficiently used in combination with the patch-clamp technique. We define a set of underlying principles governing the operation of this microscope/patch-clamp configuration and demonstrate its performance in practice using cultured astrocytes, microglia, and oligodendrocytes. Experimental results show that our custom configuration provides stable recordings, has a high success rate of the whole-cell patch-clamp trials, can be effectively applied to study cellular physiology of glial cells, and provides comparable performance and usability to the commercially available systems. Our system can be easily replicated or adapted to suit the needs of the research groups and can be cost-effective in reducing the investments in purchasing additional equipment. We provide step-by-step instructions on implementing an upright microscope with z-axis movable stage as a routine workhorse for patch-clamping.",
publisher = "Hoboken: John Wiley and Sons Inc.",
journal = "Microscopy Research and Technique",
title = "Approach for patch-clamping using an upright microscope with z-axis movable stage.",
number = "6",
volume = "85",
doi = "10.1002/jemt.24066",
pages = "2095-2104"
}
Perić, M., Bataveljić, D., Bijelić, D., Milićević, K., Andjus, P. R., Bogdanović Pristov, J.,& Nikolić, L.. (2022). Approach for patch-clamping using an upright microscope with z-axis movable stage.. in Microscopy Research and Technique
Hoboken: John Wiley and Sons Inc.., 85(6), 2095-2104.
https://doi.org/10.1002/jemt.24066
Perić M, Bataveljić D, Bijelić D, Milićević K, Andjus PR, Bogdanović Pristov J, Nikolić L. Approach for patch-clamping using an upright microscope with z-axis movable stage.. in Microscopy Research and Technique. 2022;85(6):2095-2104.
doi:10.1002/jemt.24066 .
Perić, Mina, Bataveljić, Danijela, Bijelić, Dunja, Milićević, Katarina, Andjus, Pavle R., Bogdanović Pristov, Jelena, Nikolić, Ljiljana, "Approach for patch-clamping using an upright microscope with z-axis movable stage." in Microscopy Research and Technique, 85, no. 6 (2022):2095-2104,
https://doi.org/10.1002/jemt.24066 . .
3
1
1

Naïve astrocytes react to CNS-infiltrated immune cells

Čupić, Željko; Anić, Slobodan; Milićević, Katarina; Lazarević, Milica; Momčilović, Miljana; Todorović, Nataša; Petković, Branka; Stojadinović, Gordana; Nikolić, Ljiljana

(Belgrade: Society of Physical Chemists of Serbia, 2022)

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

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

Milićević, Katarina; Bijelić, Dunja; Lazarević, Milica; Miljković, Đorđe; Bogdanović Pristov, Jelena; Petković, Branka; Anđus, Pavle; Momčilović, Miljana; Nikolić, Ljiljana

(Querétaro, México: Instituto de neurobiologia, 2020)

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

Astrocyte activity in the central nervous system autoimmunity

Nikolić, Ljiljana; Bijelić, Dunja; Lazarević, Milica; Milićević, Katarina; Momčilović, Miljana; Bogdanović Pristov, Jelena; Petković, Branka; Anđus, Pavle; Miljković, Đorđe

(Belgrade : Serbian Neuroscience Society, 2019)

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

Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line

Milićević, Katarina; Milošević, Milena; Božić, Iva; Lavrnja, Irena; Stevanović, Ivana; Bijelić, Dunja D.; Živković, Irena; Stević, Zorica; Anđus, Pavle R.

(Belgrade: Serbian Neuroscience Society, 2017)

TY  - CONF
AU  - Milićević, Katarina
AU  - Milošević, Milena
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Bijelić, Dunja D.
AU  - Živković, Irena
AU  - Stević, Zorica
AU  - Anđus, Pavle R.
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5990
AB  - Introduction. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons. Having in mind well documented facts that on one hand, ALS brain is under oxidative stress, and on the other that non-cell autonomous mechanisms involving glial cells contribute to the disease progression, we wanted to examine the effect of humoral factors immunoglobulins G from ALS patients (ALS IgG) on oxidative stress and antioxidative system of BV-2 microglial cell line. Methods. BV-2 cells were treated with ALS and control IgG (0.1 mg/ml). TNF-α release, oxidative stress markers and antioxidative enzymes activities were determined using biochemical assays (24 h treatment), while gene expression was determined using RT-qPCR (4 h treatment). ROS, cytosolic peroxide and pH alteration were evaluated with carboxy-H2DCFDA, HyPer and SypHer, respectively. Results. All tested ALS IgG (compared with control IgG) induced oxidative stress (rise in NO and lipid peroxidation), release of TNF-α and higher antioxidative defense (elevation of Mn- and Cu,Zn-superoxide dismutase, catalase, glutathione reductase with a decrease of glutathione peroxidase and glutathione). IgG from 4/11 ALS patients induced slow exponential rise of HyPer intensity and lower increase of SypHer intensity. None of the control IgG induced changes with neither of the indicators. Acute ROS generation was detected in 1/3 of ALS samples with carboxy-H2DCFDA. Conclusion. Our study demonstrates the potential role of inflammatory humoral factors, ALS IgGs, as triggers (via ROS generation) of the activation in microglia, known to occur in later stages of the disease.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
T1  - Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5990
ER  - 
@conference{
author = "Milićević, Katarina and Milošević, Milena and Božić, Iva and Lavrnja, Irena and Stevanović, Ivana and Bijelić, Dunja D. and Živković, Irena and Stević, Zorica and Anđus, Pavle R.",
year = "2017",
abstract = "Introduction. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons. Having in mind well documented facts that on one hand, ALS brain is under oxidative stress, and on the other that non-cell autonomous mechanisms involving glial cells contribute to the disease progression, we wanted to examine the effect of humoral factors immunoglobulins G from ALS patients (ALS IgG) on oxidative stress and antioxidative system of BV-2 microglial cell line. Methods. BV-2 cells were treated with ALS and control IgG (0.1 mg/ml). TNF-α release, oxidative stress markers and antioxidative enzymes activities were determined using biochemical assays (24 h treatment), while gene expression was determined using RT-qPCR (4 h treatment). ROS, cytosolic peroxide and pH alteration were evaluated with carboxy-H2DCFDA, HyPer and SypHer, respectively. Results. All tested ALS IgG (compared with control IgG) induced oxidative stress (rise in NO and lipid peroxidation), release of TNF-α and higher antioxidative defense (elevation of Mn- and Cu,Zn-superoxide dismutase, catalase, glutathione reductase with a decrease of glutathione peroxidase and glutathione). IgG from 4/11 ALS patients induced slow exponential rise of HyPer intensity and lower increase of SypHer intensity. None of the control IgG induced changes with neither of the indicators. Acute ROS generation was detected in 1/3 of ALS samples with carboxy-H2DCFDA. Conclusion. Our study demonstrates the potential role of inflammatory humoral factors, ALS IgGs, as triggers (via ROS generation) of the activation in microglia, known to occur in later stages of the disease.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia",
title = "Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line",
pages = "72",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5990"
}
Milićević, K., Milošević, M., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D. D., Živković, I., Stević, Z.,& Anđus, P. R.. (2017). Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 72.
https://hdl.handle.net/21.15107/rcub_ibiss_5990
Milićević K, Milošević M, Božić I, Lavrnja I, Stevanović I, Bijelić DD, Živković I, Stević Z, Anđus PR. Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia. 2017;:72.
https://hdl.handle.net/21.15107/rcub_ibiss_5990 .
Milićević, Katarina, Milošević, Milena, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja D., Živković, Irena, Stević, Zorica, Anđus, Pavle R., "Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line" in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia (2017):72,
https://hdl.handle.net/21.15107/rcub_ibiss_5990 .

Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line

Milošević, Milena; Milićević, Katarina; Božić, Iva; Lavrnja, Irena; Stevanović, Ivana; Bijelić, Dunja; Dubaić, Marija; Živković, Irena; Stević, Zorica; Giniatullin, Rashid; Andjus, Pavle

(2017)

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