title: Co-housing reverses memory decline by epigenetic regulation of brain-derived neurotrophic factor expression in an animal model of Alzheimer's disease.
abstract: Co-housing with a company exerts profound effects on memory decline in animal model of Alzheimer's disease (AD). Recently, we found that APP/PS1 mice of 9-month-old improved their memories after co-housing with wide-type mice for 3months by increasing hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the mechanism of how co-housing could induce BDNF expression remains elusive. Here we examined epigenetic changes in the mouse hippocampus that accompanied the co-housing-induced memory improvement. We found that the level of histone deacetylase 2 (HDAC2), but not that of HDAC1, was significantly lower in the memory improved mice than in the control and memory un-improved APP/PS1 mice after co-housing. Knockdown of Hdac2 resulted in a higher freezing response after co-housing. Conversely, over-expression of HDAC2 blocked co-housing-induced memory improvement. The level of Bdnf exon IV mRNA increased significantly after knockdown of Hdac2. ChIP assay revealed a decreased occupancy of HDAC2 in the promoter region of Bdnf exon IV of memory improved mice but not memory un-improved and control APP/PS1 mice. Consistently, the acetylation of histone 3 on Lys 9 (H3K9) and histone 4 on Lys12 (H4K12) increased significantly in the promoter region of Bdnf exon IV. These results suggest HDAC2 expression is reduced after co-housing resulting in a decreased occupancy of HDAC2 and increased histone H3K9 and H4K12 acetylation in the promoter region of Bdnf exon IV, leading to increased BDNF expression in the hippocampus that improves memory.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Ya-Hsin
authors.initials: YH
authors.lastname: Hsiao
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Yang-Jung
authors.initials: YJ
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Su
authors.affiliation: Microbiology and Immunology, College of Medicine, National Cheng Kung University, Taiwan.
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Taiwan; Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 70101, Taiwan. Electronic address: powu@mail.ncku.edu.tw.
authors.forename: Po-Wu
authors.initials: PW
authors.lastname: Gean
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006799:Housing, Animal; D008297:Male; D008569:Memory Disorders / Q000378:metabolism* / Q000523:psychology; D051379:Mice
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D056464:Histone Deacetylase 2
keywords: Alzheimer’s disease; BDNF; Epigenetic; HDAC2; Hippocampus