Epigenetic Suppression of Neuroligin 1 Underlies Amyloid-induced Memory Deficiency

Overview

Journal Nat Neurosci

Date 2014 Jan 21

PMID 24441681

Citations 56

Authors

Bihua Bie

Jiang Wu

Hui Yang

Jijun J Xu

David L Brown

Mohamed Naguib

Affiliations

Soon will be listed here.

Abstract

Amyloid-induced microglial activation and neuroinflammation impair central synapses and memory function, although the mechanism remains unclear. Neuroligin 1 (NLGN1), a postsynaptic protein found in central excitatory synapses, governs excitatory synaptic efficacy and plasticity in the brain. Here we found, in rodents, that amyloid fibril-induced neuroinflammation enhanced the interaction between histone deacetylase 2 and methyl-CpG-binding protein 2, leading to suppressed histone H3 acetylation and enhanced cytosine methylation in the Nlgn1 promoter region and decreased NLGN1 expression, underlying amyloid-induced memory deficiency. Manipulation of microglia-associated neuroinflammation modulated the epigenetic modification of the Nlgn1 promoter, hippocampal glutamatergic transmission and memory function. These findings link neuroinflammation, synaptic efficacy and memory, thus providing insight into the pathogenesis of amyloid-associated diseases.

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