GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease
By Seonmi Jo, O. Yarishkin, Y. Hwang, Y. Chun, Mijeong Park, D. H. Woo, J. Bae, Taekeun Kim, Jaekwang Lee, Heejung Chun and 18 more. Nature Medicine, 2014
691 citations recorded by the source corpus.
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.
Subfields: Biological Psychiatry, Neurology, Physiology
View Paper: https://www.semanticscholar.org/paper/53fcf370b9a3db993dae6c5335932946d8fefb41
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Citations in the corpus
- Astrocytes: a central element in neurological diseases (2016, neutral): “mice [103].”
- Inflammation as a central mechanism in Alzheimer's disease (2018, background): “[181] Jo S, Yarishkin O, Hwang YJ, Chun YE, Park M, Woo DH, et al.”
- Spermidine in health and disease (2018, background): “This MAOB activity favors the conversion of putrescine to the gliotransmitter g-aminobutyric acid (GABA), which drives Alzheimer’s-associated pathology in APP/PS1 mice that carry mutations in the amyloid precursor protein (APP) and the g-secretase presenilin-1 (PS1) (119).”