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Nat Commun. 2014 Jun 13;5:4159. doi: 10.1038/ncomms5159.

Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer's [corrected] disease model.

Author information

1
Department of Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
2
Department of Pathology and Laboratory Medicine, Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Erratum in

  • Nat Commun. 2014;5:4810.

Abstract

Amyloid plaques and tau tangles are common pathological hallmarks for Alzheimer's disease (AD); however, reducing Aβ production failed to relieve the symptoms of AD patients. Here we report a high GABA (γ-aminobutyric acid) content in reactive astrocytes in the dentate gyrus (DG) of a mouse model for AD (5xFAD) that results in increased tonic inhibition and memory deficit. We also confirm in human AD patient brains that dentate astrocytes have a high GABA content, suggesting that high astrocytic GABA level may be a novel biomarker and a potential diagnostic tool for AD. The excessive GABA in 5xFAD astrocytes is released through an astrocyte-specific GABA transporter GAT3/4, and significantly enhances tonic GABA inhibition in dentate granule cells. Importantly, reducing tonic inhibition in 5xFAD mice rescues the impairment of long-term potentiation (LTP) and memory deficit. Thus, reducing tonic GABA inhibition in the DG may lead to a novel therapy for AD.

PMID:
24923909
PMCID:
PMC4159602
DOI:
10.1038/ncomms5159
[Indexed for MEDLINE]
Free PMC Article

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