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标题：Premature aging of the hippocampal neurogenic niche in adult Bmal1-deficient mice
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作者：Amira A. H. Ali ; Beryl Schwarz-Herzke ; Anna Stahr 等
期刊名称：Aging
出版年度：2015
卷号：7
期号：6
页码：435-449
出版社：U.S.Department of Health & Human Service
摘要：Hippocampal neurogenesis undergoes dramatic age-related changes. Mice with targeted deletion of the clock geneBmal1 (Bmal1^-/-) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1^-/- mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1^-/- mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70kDa and expression of the cell cycle inhibitor p21 ^Waf1/CIP1 were increased in adult Bmal1^-/-mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age-dependent decline in adult neurogenesis presumably as a consequence of oxidative stress.
关键词：adult neurogenesis; clock genes; dentate gyrus; bromodeoxyuridine; oxidative stress; Sirt1; PMP70; circadian disruption