GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease

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dc.contributor.authorJo, Seonmiko
dc.contributor.authorYarishkin, Olegko
dc.contributor.authorHwang, Yu Jinko
dc.contributor.authorChun, Ye Eunko
dc.contributor.authorPark, Mijeongko
dc.contributor.authorWoo, Dong Hoko
dc.contributor.authorBae, Jin Youngko
dc.contributor.authorKim, Taekeunko
dc.contributor.authorLee, Jaekwangko
dc.contributor.authorChun, Heejungko
dc.contributor.authorPark, Hyun Jungko
dc.contributor.authorLee, Da Yongko
dc.contributor.authorHong, Jinpyoko
dc.contributor.authorKim, Hye Yunko
dc.contributor.authorOh, Soo-Jinko
dc.contributor.authorPark, Seung Juko
dc.contributor.authorLee, Hyoko
dc.contributor.authorYoon, Bo-Eunko
dc.contributor.authorKim, YoungSooko
dc.contributor.authorJeong, Yongko
dc.contributor.authorShim, Insopko
dc.contributor.authorBae, Yong Chulko
dc.contributor.authorCho, Jeiwonko
dc.contributor.authorKowall, Neil W.ko
dc.contributor.authorRyu, Hoonko
dc.contributor.authorHwang, Eunmiko
dc.contributor.authorKim, Daesooko
dc.contributor.authorLee, C. Justinko
dc.date.accessioned2014-12-09T01:21:55Z-
dc.date.available2014-12-09T01:21:55Z-
dc.date.created2014-07-01-
dc.date.created2014-07-01-
dc.date.issued2014-08-
dc.identifier.citationNATURE MEDICINE, v.20, no.8, pp.886 - 896-
dc.identifier.issn1078-8956-
dc.identifier.urihttp://hdl.handle.net/10203/192365-
dc.description.abstractIn Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.subjectMONOAMINE-OXIDASE-B-
dc.subjectQUANTITATIVE ENZYME AUTORADIOGRAPHY-
dc.subjectMAO-B-
dc.subjectCULTURED ASTROCYTES-
dc.subjectGLUTAMATE RELEASE-
dc.subjectTRANSGENIC MOUSE-
dc.subjectSENILE PLAQUES-
dc.subjectDENTATE GYRUS-
dc.subjectL-DEPRENYL-
dc.subjectSELEGILINE-
dc.titleGABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease-
dc.typeArticle-
dc.identifier.wosid000340074600020-
dc.identifier.scopusid2-s2.0-84905822105-
dc.type.rimsART-
dc.citation.volume20-
dc.citation.issue8-
dc.citation.beginningpage886-
dc.citation.endingpage896-
dc.citation.publicationnameNATURE MEDICINE-
dc.identifier.doi10.1038/nm.3639-
dc.contributor.localauthorJeong, Yong-
dc.contributor.localauthorKim, Daesoo-
dc.contributor.nonIdAuthorYarishkin, Oleg-
dc.contributor.nonIdAuthorHwang, Yu Jin-
dc.contributor.nonIdAuthorChun, Ye Eun-
dc.contributor.nonIdAuthorPark, Mijeong-
dc.contributor.nonIdAuthorWoo, Dong Ho-
dc.contributor.nonIdAuthorBae, Jin Young-
dc.contributor.nonIdAuthorKim, Taekeun-
dc.contributor.nonIdAuthorLee, Jaekwang-
dc.contributor.nonIdAuthorChun, Heejung-
dc.contributor.nonIdAuthorPark, Hyun Jung-
dc.contributor.nonIdAuthorLee, Da Yong-
dc.contributor.nonIdAuthorHong, Jinpyo-
dc.contributor.nonIdAuthorKim, Hye Yun-
dc.contributor.nonIdAuthorOh, Soo-Jin-
dc.contributor.nonIdAuthorPark, Seung Ju-
dc.contributor.nonIdAuthorLee, Hyo-
dc.contributor.nonIdAuthorYoon, Bo-Eun-
dc.contributor.nonIdAuthorKim, YoungSoo-
dc.contributor.nonIdAuthorShim, Insop-
dc.contributor.nonIdAuthorBae, Yong Chul-
dc.contributor.nonIdAuthorCho, Jeiwon-
dc.contributor.nonIdAuthorKowall, Neil W.-
dc.contributor.nonIdAuthorRyu, Hoon-
dc.contributor.nonIdAuthorHwang, Eunmi-
dc.contributor.nonIdAuthorLee, C. Justin-
dc.type.journalArticleArticle-
dc.subject.keywordPlusMONOAMINE-OXIDASE-B-
dc.subject.keywordPlusQUANTITATIVE ENZYME AUTORADIOGRAPHY-
dc.subject.keywordPlusMAO-B-
dc.subject.keywordPlusCULTURED ASTROCYTES-
dc.subject.keywordPlusGLUTAMATE RELEASE-
dc.subject.keywordPlusTRANSGENIC MOUSE-
dc.subject.keywordPlusSENILE PLAQUES-
dc.subject.keywordPlusDENTATE GYRUS-
dc.subject.keywordPlusL-DEPRENYL-
dc.subject.keywordPlusSELEGILINE-
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BiS-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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