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Bestrophin1-mediated tonic GABA release from reactive astrocytes prevents the development of seizure-prone network in kainate-injected hippocampi

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Title
Bestrophin1-mediated tonic GABA release from reactive astrocytes prevents the development of seizure-prone network in kainate-injected hippocampi
Author(s)
Pandit S.; Neupane C.; Woo J.; Sharma R.; Nam M.-H.; Lee G.-S.; Yi M.-H.; Shin N.; Kim D.W.; Cho H.; Jeon B.H.; Kim H.-W.; C. Justin Lee; Park J.B.
Publication Date
2020-05
Journal
GLIA, v.68, no.5, pp.1065 - 1080
Publisher
WILEY-BLACKWELL
Abstract
© 2019 Wiley Periodicals, Inc.Tonic extrasynaptic GABAA receptor (GABAAR) 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
URI
https://pr.ibs.re.kr/handle/8788114/7098
ISSN
0894-1491
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Cognitive Glioscience Group(인지 교세포과학 그룹) > Journal Papers (저널논문)
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