title: Premature aging of the hippocampal neurogenic niche in adult Bmal1-deficient mice.
abstract: 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 70 kDa 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.
authors.affiliation: Institute for Anatomy II, Medical Faculty, Heinrich Heine University, D-40225, Düsseldorf, Germany.
authors.forename: Amira A H
authors.initials: AA
authors.lastname: Ali
authors.affiliation: Institute for Anatomy II, Medical Faculty, Heinrich Heine University, D-40225, Düsseldorf, Germany.
authors.forename: Beryl
authors.initials: B
authors.lastname: Schwarz-Herzke
authors.affiliation: Institute for Anatomy II, Medical Faculty, Heinrich Heine University, D-40225, Düsseldorf, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Stahr
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Timour
authors.initials: T
authors.lastname: Prozorovski
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.affiliation: Institute for Anatomy II, Medical Faculty, Heinrich Heine University, D-40225, Düsseldorf, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: von Gall
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D019588:Aging, Premature; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; D018528:ATP-Binding Cassette Transporters; C489271:Abcd3 protein, mouse; C538961:Bmal1 protein, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: PMP70; Sirt1; adult neurogenesis; bromodeoxyuridine; circadian disruption; clock genes; dentate gyrus; oxidative stress