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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Nikolić, Ljiljana
AU  - Shen, Weida
AU  - Nobili, Paola
AU  - Virenque, Anaïs
AU  - Ulmann, Lauriane
AU  - Audinat, Etienne
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5516
AB  - Epilepsy is characterized by unpredictable recurrent seizures resulting from abnormal neuronal excitability. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability, but the underlying mechanism that alters glial signaling in epilepsy remains unknown. Increase in glutamate release by astrocytes partici- pates in the onset and progression of seizures. Epileptic seizures are also accompanied by increase of tumor necrosis factor alpha (TNFα), a cytokine involved in the regulation of astrocyte glutamate release. Here we tested whether TNFα controls abnormal astrocyte glutamate signal- ing in epilepsy and through which mechanism. Combining Ca2+ imaging, optogenetics, and elec- trophysiology, we report that TNFα triggers a Ca2+-dependent glutamate release from astrocytes that boosts excitatory synaptic activity in the hippocampus through a mechanism involving autocrine activation of P2Y1 receptors by astrocyte-derived ATP/ADP. In a mouse model of temporal lobe epilepsy, such TNFα-driven astrocytic purinergic signaling is perma- nently active, promotes glial glutamate release, and drives abnormal synaptic activity in the hip- pocampus. Blocking this pathway by inhibiting P2Y1 receptors restores normal excitatory synaptic activity in the inflamed hippocampus. Our findings indicate that targeting the coupling of TNFα with astrocyte purinergic signaling may be a therapeutic strategy for reducing glial glu- tamate release and normalizing synaptic activity in epilepsy.
PB  - Hoboken : John Wiley & Sons Ltd
T2  - Glia
T1  - Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy
IS  - 12
VL  - 66
DO  - 10.1002/glia.23519
SP  - 2673
EP  - 2683
ER  - 

@article{
author = "Nikolić, Ljiljana and Shen, Weida and Nobili, Paola and Virenque, Anaïs and Ulmann, Lauriane and Audinat, Etienne",
year = "2018",
abstract = "Epilepsy is characterized by unpredictable recurrent seizures resulting from abnormal neuronal excitability. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability, but the underlying mechanism that alters glial signaling in epilepsy remains unknown. Increase in glutamate release by astrocytes partici- pates in the onset and progression of seizures. Epileptic seizures are also accompanied by increase of tumor necrosis factor alpha (TNFα), a cytokine involved in the regulation of astrocyte glutamate release. Here we tested whether TNFα controls abnormal astrocyte glutamate signal- ing in epilepsy and through which mechanism. Combining Ca2+ imaging, optogenetics, and elec- trophysiology, we report that TNFα triggers a Ca2+-dependent glutamate release from astrocytes that boosts excitatory synaptic activity in the hippocampus through a mechanism involving autocrine activation of P2Y1 receptors by astrocyte-derived ATP/ADP. In a mouse model of temporal lobe epilepsy, such TNFα-driven astrocytic purinergic signaling is perma- nently active, promotes glial glutamate release, and drives abnormal synaptic activity in the hip- pocampus. Blocking this pathway by inhibiting P2Y1 receptors restores normal excitatory synaptic activity in the inflamed hippocampus. Our findings indicate that targeting the coupling of TNFα with astrocyte purinergic signaling may be a therapeutic strategy for reducing glial glu- tamate release and normalizing synaptic activity in epilepsy.",
publisher = "Hoboken : John Wiley & Sons Ltd",
journal = "Glia",
title = "Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy",
number = "12",
volume = "66",
doi = "10.1002/glia.23519",
pages = "2673-2683"
}

Nikolić, L., Shen, W., Nobili, P., Virenque, A., Ulmann, L.,& Audinat, E.. (2018). Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy. in Glia
Hoboken : John Wiley & Sons Ltd., 66(12), 2673-2683.
https://doi.org/10.1002/glia.23519

Nikolić L, Shen W, Nobili P, Virenque A, Ulmann L, Audinat E. Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy. in Glia. 2018;66(12):2673-2683.
doi:10.1002/glia.23519 .

Nikolić, Ljiljana, Shen, Weida, Nobili, Paola, Virenque, Anaïs, Ulmann, Lauriane, Audinat, Etienne, "Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy" in Glia, 66, no. 12 (2018):2673-2683,
https://doi.org/10.1002/glia.23519 . .

TY  - JOUR
AU  - Nikolić, Ljiljana
AU  - Shen, Weida
AU  - Nobili, Paola
AU  - Virenque, Anaïs
AU  - Ulmann, Lauriane
AU  - Audinat, Etienne
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5515
AB  - Epilepsy is characterized by unpredictable recurrent seizures resulting from abnormal neuronal excitability. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability, but the underlying mechanism that alters glial signaling in epilepsy remains unknown. Increase in glutamate release by astrocytes partici- pates in the onset and progression of seizures. Epileptic seizures are also accompanied by increase of tumor necrosis factor alpha (TNFα), a cytokine involved in the regulation of astrocyte glutamate release. Here we tested whether TNFα controls abnormal astrocyte glutamate signal- ing in epilepsy and through which mechanism. Combining Ca2+ imaging, optogenetics, and elec- trophysiology, we report that TNFα triggers a Ca2+-dependent glutamate release from astrocytes that boosts excitatory synaptic activity in the hippocampus through a mechanism involving autocrine activation of P2Y1 receptors by astrocyte-derived ATP/ADP. In a mouse model of temporal lobe epilepsy, such TNFα-driven astrocytic purinergic signaling is perma- nently active, promotes glial glutamate release, and drives abnormal synaptic activity in the hip- pocampus. Blocking this pathway by inhibiting P2Y1 receptors restores normal excitatory synaptic activity in the inflamed hippocampus. Our findings indicate that targeting the coupling of TNFα with astrocyte purinergic signaling may be a therapeutic strategy for reducing glial glu- tamate release and normalizing synaptic activity in epilepsy.
PB  - Hoboken : John Wiley & Sons Ltd
T2  - Glia
T1  - Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy
IS  - 12
VL  - 66
DO  - 10.1002/glia.23519
SP  - 2673
EP  - 2683
ER  - 

@article{
author = "Nikolić, Ljiljana and Shen, Weida and Nobili, Paola and Virenque, Anaïs and Ulmann, Lauriane and Audinat, Etienne",
year = "2018",
abstract = "Epilepsy is characterized by unpredictable recurrent seizures resulting from abnormal neuronal excitability. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability, but the underlying mechanism that alters glial signaling in epilepsy remains unknown. Increase in glutamate release by astrocytes partici- pates in the onset and progression of seizures. Epileptic seizures are also accompanied by increase of tumor necrosis factor alpha (TNFα), a cytokine involved in the regulation of astrocyte glutamate release. Here we tested whether TNFα controls abnormal astrocyte glutamate signal- ing in epilepsy and through which mechanism. Combining Ca2+ imaging, optogenetics, and elec- trophysiology, we report that TNFα triggers a Ca2+-dependent glutamate release from astrocytes that boosts excitatory synaptic activity in the hippocampus through a mechanism involving autocrine activation of P2Y1 receptors by astrocyte-derived ATP/ADP. In a mouse model of temporal lobe epilepsy, such TNFα-driven astrocytic purinergic signaling is perma- nently active, promotes glial glutamate release, and drives abnormal synaptic activity in the hip- pocampus. Blocking this pathway by inhibiting P2Y1 receptors restores normal excitatory synaptic activity in the inflamed hippocampus. Our findings indicate that targeting the coupling of TNFα with astrocyte purinergic signaling may be a therapeutic strategy for reducing glial glu- tamate release and normalizing synaptic activity in epilepsy.",
publisher = "Hoboken : John Wiley & Sons Ltd",
journal = "Glia",
title = "Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy",
number = "12",
volume = "66",
doi = "10.1002/glia.23519",
pages = "2673-2683"
}

Nikolić, L., Shen, W., Nobili, P., Virenque, A., Ulmann, L.,& Audinat, E.. (2018). Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy. in Glia
Hoboken : John Wiley & Sons Ltd., 66(12), 2673-2683.
https://doi.org/10.1002/glia.23519

Nikolić L, Shen W, Nobili P, Virenque A, Ulmann L, Audinat E. Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy. in Glia. 2018;66(12):2673-2683.
doi:10.1002/glia.23519 .

Nikolić, Ljiljana, Shen, Weida, Nobili, Paola, Virenque, Anaïs, Ulmann, Lauriane, Audinat, Etienne, "Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity in epilepsy" in Glia, 66, no. 12 (2018):2673-2683,
https://doi.org/10.1002/glia.23519 . .