Paper Chase is a research database designed to offer abstracts of research articles published in journals that have a highly rated impact factor as determined by ISI Impact Factor and PageRank. Abstracts are organized by date, with the most recently published papers listed first.
GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease.
Nat. Med..06 29, 2014;20(8):886-96.
Jo S, Yarishkin O, Hwang YJ, Chun YE, Park M, Woo DH, Bae JY, Kim T, Lee J, Chun H, Park HJ, Lee da Y, Hong J, Kim HY, Oh SJ, Park SJ, Lee H, Yoon BE, Kim Y, Jeong Y, Shim I, Bae YC, Cho J, Kowall NW, Ryu H, Hwang E, Kim D, Lee CJ.
1] WCI Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.  Neuroscience Program, Korea University of Science and Technology, Daejeon, Republic of Korea.  Center for Neuroscience, Brain Science Institute, KIST, Seoul, Republic of Korea.  KU-KIST Graduate School of Converging Science of Technology, Korea University, Seoul, Republic of Korea.
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.