期刊
CELL REPORTS
卷 32, 期 1, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.107861
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资金
- Creative Research Initiative Program - National Research Foundation (NRF) of Korea [2015R1A3A2066619]
- Institute for Basic Science (IBS), Center for Cognition and Sociality [IBS-R001-D2]
- Basic Science Research Program - NRF of Korea [NRF-2016R1A2B3009660]
- Biomedical Integrated Technology Research Project - GIST
- KIST institutional program through Korea Institute of Science and Technology - Ministry of Science and ICT of Korea [2E30180]
- National Research Foundation of Korea [2015R1A3A2066619] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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