Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency

被引:90
作者
Bie, Bihua [1 ]
Wu, Jiang [1 ]
Yang, Hui [1 ]
Xu, Jijun J. [1 ]
Brown, David L. [1 ]
Naguib, Mohamed [1 ]
机构
[1] Cleveland Clin, Inst Anesthesiol, Dept Gen Anesthesiol, Cleveland, OH 44106 USA
关键词
CPG-BINDING-PROTEIN; INHIBITORY SYNAPSE FORMATION; NERVE GROWTH-FACTOR; ALZHEIMERS-DISEASE; SPATIAL MEMORY; HISTONE DEACETYLASE; MYELOID CELLS; A-BETA; MECP2; PHOSPHORYLATION;
D O I
10.1038/nn.3618
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:223 / 231
页数:9
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