Memory Impairment Induced by Borna Disease Virus 1 Infection is Associated with Reduced H3K9 Acetylation
Autor: | Jie Jie, Xiaoyan Xu, Yujie Guo, Zhe Tu, Xiong Zhang, Haiyang Wang, Chenmeng Li, Weihong Song, Peng Xie, Jinjun Xia |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Chromatin Immunoprecipitation Physiology Morris water navigation task Hydroxamic Acids Synaptic plasticity lcsh:Physiology Chromatin remodeling lcsh:Biochemistry Histones Rats Sprague-Dawley 03 medical and health sciences Neurotrophic factors Memory Animals lcsh:QD415-436 Epigenetics H3K9 acetylation Borna disease virus Maze Learning Borna Disease Virus 1 Cells Cultured Neurons Vorinostat Neuronal Plasticity lcsh:QP1-981 biology Brain-Derived Neurotrophic Factor Acetylation Memory impairment Chromatin Cell biology Rats Disease Models Animal 030104 developmental biology Histone Borna Disease biology.protein Disks Large Homolog 4 Protein |
Zdroj: | Cellular Physiology and Biochemistry, Vol 49, Iss 1, Pp 381-394 (2018) |
ISSN: | 1421-9778 |
Popis: | Background/Aims: Borna disease virus 1 (BoDV-1) infection induces cognitive impairment in rodents. Emerging evidence has demonstrated that Chromatin remodeling through histone acetylation can regulate cognitive function. In the present study, we investigated the epigenetic regulation of chromatin that underlies BoDV-1-induced cognitive changes in the hippocampus. Methods: Immunofluorescence assay was applied to detect BoDV-1 infection in hippocampal neurons and Sprague-Dawley rats models. The histone acetylation levels both in vivo and vitro were assessed by western blots. The acetylation-regulated genes were identified by ChIP-seq and verified by RT-qPCR. Cognitive functions were evaluated with Morris Water Maze test. In addition, Golgi staining, and electrophysiology were used to study changes in synaptic structure and function. Results: BoDV-1 infection of hippocampal neurons significantly decreased H3K9 histone acetylation level and inhibited transcription of several synaptic genes, including postsynaptic density 95 (PSD95) and brain-derived neurotrophic factor (BDNF). Furthermore, BoDV-1 infection of Sprague Dawley rats disrupted synaptic plasticity and caused spatial memory impairment. These rats also exhibited dysregulated hippocampal H3K9 acetylation and decreased PSD95 and BDNF protein expression. Treatment with the HDAC inhibitor, suberanilohydroxamic acid (SAHA), attenuated the negative effects of BoDV-1. Conclusion: Our results demonstrate that regulation of H3K9 histone acetylation may play an important role in BoDV-1-induced memory impairment, whereas SAHA may confer protection against BoDV-1-induced cognitive impairments. This study finds important mechanism of BoDV-1 infection disturbing neuronal synaptic plasticity and inducing cognitive dysfunction from the perspective of histone modification. |
Databáze: | OpenAIRE |
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