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

Title
GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease
Authors
조선미올레그황유진천예은박미정우동호배진영김태근이재광전희정박현정이다용홍진표김혜연오수진박승주이효윤보은김영수정용심인섭배용철조제원Neil W Kowall류훈황은미김대수이창준
Issue Date
2014-08
Publisher
Nature medicine
Citation
VOL 20, NO 8, 886-896
Abstract
In 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.
URI
http://pubs.kist.re.kr/handle/201004/47784
ISSN
10788956
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE