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 . .