Pandit, Sudip Neupane, Chiranjivi Woo, Junsung Sharma, Ramesh Nam, Min-Ho Lee, Gyu-Seung Yi, Min-Hee Shin, Nara Kim, Dong Woon Cho, Hyunsill Jeon, Byeong Hwa Kim, Hyun-Woo Lee, C. Justin Park, Jin Bong 2024-01-19T17:33:21Z 2024-01-19T17:33:21Z 2021-09-05 2020-05 0894-1491 https://pubs.kist.re.kr/handle/201004/118664 Tonic extrasynaptic GABA(A) receptor (GABA(A)R) activation is under the tight control of tonic GABA release from astrocytes to maintain the brain's excitation/inhibition (E/I) balance; any slight E/I balance disturbance can cause serious pathological conditions including epileptic seizures. However, the pathophysiological role of tonic GABA release from astrocytes has not been tested in epileptic seizures. Here, we report that pharmacological or genetic intervention of the GABA-permeable Bestrophin-1 (Best1) channel prevented the generation of tonic GABA inhibition, disinhibiting CA1 pyramidal neuronal firing and augmenting seizure susceptibility in kainic acid (KA)-induced epileptic mice. Astrocyte-specific Best1 over-expression in KA-injected Best1 knockout mice fully restored the generation of tonic GABA inhibition and effectively suppressed seizure susceptibility. We demonstrate for the first time that tonic GABA from reactive astrocytes strongly contributes to the compensatory shift of E/I balance in epileptic hippocampi, serving as a good therapeutic target against altered E/I balance in epileptic seizures. English WILEY DENTATE GRANULE CELLS KAINIC ACID INHIBITORY NEUROTRANSMISSION ALZHEIMERS-DISEASE MOUSE MODEL GLIAL GABA GYRUS RECEPTORS TRANSPORTER MODULATION Bestrophin1-mediated tonic GABA release from reactive astrocytes prevents the development of seizure-prone network in kainate-injected hippocampi Article 10.1002/glia.23762 1 GLIA, v.68, no.5, pp.1065 - 1080 GLIA 68 5 1065 1080 scie scopus 000502395200001 2-s2.0-85076338994 Neurosciences Neurosciences & Neurology Article DENTATE GRANULE CELLS KAINIC ACID INHIBITORY NEUROTRANSMISSION ALZHEIMERS-DISEASE MOUSE MODEL GLIAL GABA GYRUS RECEPTORS TRANSPORTER MODULATION Bestrophin1 hippocampus reactive astrocytes seizure tonic GABA