Emory University2014-07-18 5:04 PM

Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzhiemer’s disease model

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.

full article:
http://www.nature.com/ncomms/2014/140613/ncomms5159/full/ncomms5159.html

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

Emory University

0 Following 0 Fans 0 Projects 3 Articles

SIMILAR ARTICLES

AbstractBackground Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. W

Read More

AbstractAmyloid plaques and tau tangles are common pathological hallmarks for Alzheimer’s disease (AD); however, reducing Aβ production failed to relie

Read More

Keywords:Dialysis facilities;ESRD Networks;kidney transplantationAbstractVariability in transplant rates between different dialysis units has been note

Read More