Excessive astrocytic GABA causes cortical hypometabolism and impedes functional recovery following subcortical stroke

Title
Excessive astrocytic GABA causes cortical hypometabolism and impedes functional recovery following subcortical stroke
Authors
오수진박기덕남민호최지원조종욱권대혁박지영우준성이정무이상원고해영원우진김라경송한림박은경정혜진김형석이민철윤미진이창준김형일
Issue Date
2020-07
Publisher
Cell Reports
Abstract
Glucose hypometabolism in cortical structures after functional disconnection is frequently reported in patients with white matter diseases such as subcortical stroke. However, the molecular and cellular mechanisms have been poorly elucidated. Here we show, in an animal model of internal capsular infarct, that GABA-synthesizing reactive astrocytes in distant cortical areas cause glucose hypometabolism via tonic inhibition of neighboring neurons. We find that reversal of aberrant astrocytic GABA synthesis, by pharmacological inhibition and astrocyte-specific gene silencing of MAO-B, reverses the reduction in cortical glucose metabolism. Moreover, induction of aberrant astrocytic GABA synthesis by cortical injection of putrescine or adenovirus recapitulates cortical hypometabolism. Furthermore, MAO-B inhibition causes a remarkable recovery from post-stroke motor deficits when combined with a rehabilitation regimen. Collectively, our data indicate that cortical glucose hypometabolism in subcortical stroke is caused by aberrant astrocytic GABA and MAO-B inhibition and that attenuating cortical hypometabolism can be a therapeutic approach in subcortical stroke.
URI
http://pubs.kist.re.kr/handle/201004/63569
ISSN
2211-1247
Appears in Collections:
KIST Publication > Article
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