title: Social interaction rescues memory deficit in an animal model of Alzheimer's disease by increasing BDNF-dependent hippocampal neurogenesis.
abstract: It has been recognized that the risk of cognitive decline during aging can be reduced if one maintains strong social connections, yet the neural events underlying this beneficial effect have not been rigorously studied. Here, we show that amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice demonstrate improvement in memory after they are cohoused with wild-type mice. The improvement was associated with increased protein and mRNA levels of BDNF in the hippocampus. Concomitantly, the number of BrdU(+)/NeuN(+) cells in the hippocampal dentate gyrus was significantly elevated after cohousing. Methylazoxymethanol acetate, a cell proliferation blocker, markedly reduced BrdU(+) and BrdU/NeuN(+) cells and abolished the effect of social interaction. Selective ablation of mitotic neurons using diphtheria toxin (DT) and a retrovirus vector encoding DT receptor abolished the beneficial effect of cohousing. Knockdown of BDNF by shRNA transfection blocked, whereas overexpression of BDNF mimicked the memory-improving effect. A tropomyosin-related kinase B agonist, 7,8-dihydroxyflavone, occluded the effect of social interaction. These results demonstrate that increased BDNF expression and neurogenesis in the hippocampus after cohousing underlie the reversal of memory deficit in APP/PS1 mice.
authors.affiliation: Department of Pharmacology, College of Medicine.
authors.forename: Ya-Hsin
authors.initials: YH
authors.lastname: Hsiao
authors.affiliation: Institute of Basic Medical Science, and.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, College of Medicine, Institute of Basic Medical Science, and powu@mail.ncku.edu.tw.
authors.forename: Po-Wu
authors.identifier: http://orcid.org/0000-0003-4997-6381
authors.initials: PW
authors.lastname: Gean
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018891:Dentate Gyrus / Q000502:physiology; D004167:Diphtheria Toxin / Q000494:pharmacology; D004195:Disease Models, Animal; D047309:Flavones / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D006799:Housing, Animal; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000628:therapy*; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D053764:Presenilin-1 / Q000235:genetics; D012919:Social Behavior
chemical_list: C485383:6,7-dihydroxyflavone; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D004167:Diphtheria Toxin; D047309:Flavones; D053764:Presenilin-1; C580804:presenilin 1, mouse; D008746:Methylazoxymethanol Acetate
keywords: APP/PS1 mice; Alzheimer's disease; BDNF; adult neurogenesis; memory decline; social interaction