PMID- 30138929 OWN - NLM STAT- MEDLINE DCOM- 20180918 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 49 IP - 1 DP - 2018 TI - Memory Impairment Induced by Borna Disease Virus 1 Infection is Associated with Reduced H3K9 Acetylation. PG - 381-394 LID - 10.1159/000492890 [doi] AB - 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. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Jie, Jie AU - Jie J AD - Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. FAU - Xu, Xiaoyan AU - Xu X AD - Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. FAU - Xia, Jinjun AU - Xia J AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. AD - Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China. FAU - Tu, Zhe AU - Tu Z AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. AD - Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China. FAU - Guo, Yujie AU - Guo Y AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. FAU - Li, Chenmeng AU - Li C AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. FAU - Zhang, Xiong AU - Zhang X AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. FAU - Wang, Haiyang AU - Wang H AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. FAU - Song, Weihong AU - Song W AD - Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, Vancouver, British Columbia, Canada. FAU - Xie, Peng AU - Xie P AD - Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. AD - Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. AD - Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20180823 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Disks Large Homolog 4 Protein) RN - 0 (Histones) RN - 0 (Hydroxamic Acids) RN - 58IFB293JI (Vorinostat) SB - IM MH - Acetylation/drug effects MH - Animals MH - Borna Disease/*pathology/virology MH - Borna disease virus/*physiology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cells, Cultured MH - Chromatin Immunoprecipitation MH - Disease Models, Animal MH - Disks Large Homolog 4 Protein/metabolism MH - Histones/*metabolism MH - Hydroxamic Acids/pharmacology MH - Maze Learning MH - Memory/drug effects/*physiology MH - Neuronal Plasticity/genetics MH - Neurons/cytology/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Vorinostat OTO - NOTNLM OT - Borna Disease Virus 1 OT - H3K9 acetylation OT - Memory impairment OT - Synaptic plasticity EDAT- 2018/08/24 06:00 MHDA- 2018/09/19 06:00 CRDT- 2018/08/24 06:00 PHST- 2018/01/17 00:00 [received] PHST- 2018/08/14 00:00 [accepted] PHST- 2018/08/24 06:00 [pubmed] PHST- 2018/09/19 06:00 [medline] PHST- 2018/08/24 06:00 [entrez] AID - 000492890 [pii] AID - 10.1159/000492890 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;49(1):381-394. doi: 10.1159/000492890. Epub 2018 Aug 23.