GABA from reactive astrocytes impairs learning and memory in Alzheimer disease = 반응성 성상교세포의 GABA에 의한 알츠하이머 기억장애 연구

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In Alzheimer disease, memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the original findings by Dr. Alzheimer, 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 the GABA through Best1 channel. In the dentate gyrus of mouse models of Alzheimer disease, 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 postmortem brain of individuals with Alzheimer disease, astrocytic GABA and MAOB are significantly up-regulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in Alzheimer disease.
Advisors
김대수researcherKim, Daesooresearcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2014
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2014.8,[140 p. :]

Keywords

알츠하이머병; 반응성 성상교세포; 가바; 기억; 마오B; Alzheimer disease; reactive astrocyte; GABA; memory; MAOB

URI
http://hdl.handle.net/10203/241829
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=669239&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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