한빛사논문, 상위피인용논문
Abstract
Seonmi Jo1,2,13, Oleg Yarishkin2,13, Yu Jin Hwang3, Ye Eun Chun2,4, Mijeong Park4,5, Dong Ho Woo2, Jin Young Bae6, Taekeun Kim2, Jaekwang Lee2, Heejung Chun2, Hyun Jung Park7, Da Yong Lee2, Jinpyo Hong2, Hye Yun Kim3, Soo-Jin Oh5, Seung Ju Park2, Hyo Lee2, Bo-Eun Yoon2, YoungSoo Kim3, Yong Jeong8, Insop Shim7, Yong Chul Bae6, Jeiwon Cho4,5, Neil W Kowall9.11, Hoon Ryu3,9.11, Eunmi Hwang2, Daesoo Kim1 & C Justin Lee2,4,5,12
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. 2WCI Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea. 3Center for Neuro-Medicine, Brain Science Institute, KIST, Seoul, Republic of Korea. 4Neuroscience Program, Korea University of Science and Technology, Daejeon, Republic of Korea. 5Center for Neuroscience, Brain Science Institute, KIST, Seoul, Republic of Korea. 6Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea. 7Department of Science in Korean Medicine, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea. 8Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea. 9Boston University Alzheimer’s Disease Center, Boston University School of Medicine, Boston, Massachusetts, USA. 10Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA. 11VA Boston Healthcare System, Boston, Massachusetts, USA. 12KU-KIST Graduate School of Converging Science of Technology, Korea University, Seoul, Republic of Korea.13These authors contributed equally to this work.
Correspondence to: C Justin Lee or Daesoo Kim
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.
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