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Excessive Astrocytic GABA Causes Cortical Hypometabolism and Impedes Functional Recovery after Subcortical Stroke

Authors
 Min-Ho Nam  ;  Jongwook Cho  ;  Dae-Hyuk Kwon  ;  Ji-Young Park  ;  Junsung Woo  ;  Jung Moo Lee  ;  Sangwon Lee  ;  Hae Young Ko  ;  Woojin Won  ;  Ra Gyung Kim  ;  Hanlim Song  ;  Soo-Jin Oh  ;  Ji Won Choi  ;  Ki Duk Park  ;  Eun Kyung Park  ;  Haejin Jung  ;  Hyung-Seok Kim  ;  Min-Cheol Lee  ;  Mijin Yun  ;  C Justin Lee  ;  Hyoung-Ihl Kim 
Citation
 CELL REPORTS, Vol.32(1) : 107861, 2020-07 
Journal Title
 CELL REPORTS 
Issue Date
2020-07
Keywords
GABA ; PET imaging ; astrocyte ; diaschisis ; internal capsule ; monoamine oxidase B ; reactive astrocyte ; rehabilitation ; stroke
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.
Files in This Item:
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DOI
10.1016/j.celrep.2020.107861
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180430
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