title: Changes in hippocampal neurogenesis throughout early development.
abstract: Adult hippocampal neurogenesis drastically diminishes with age but the underlying mechanisms remain unclear. Here, age-related influences on the hippocampal early neuroprogenitor cell (NPC) pool was examined by quantifying changes in Sox1-expressing cells in the dentate gyrus subgranular zone from early adulthood (3 months) to middle age (12 months). Proliferation of distinct NPC subpopulations (Sox1+, Nestin+, and Doublecortin+) and newborn cell survival were also investigated. Examination of total 5-bromodeoxyuridine (BrdU)+ and Doublecortin (DCX)± cells revealed an early and dramatic age-dependent decline of hippocampal neurogenesis. Increasing age from 3 to 12 months was primarily associated with reduced total proliferation, in vivo (-79% of BrdU+ cells) but not in vitro, and DCX+ cell numbers (-89%). When proliferative rates of individual NPC subpopulations were examined, a different picture emerged as proliferating Nestin+ neuroprogenitors (-95% at 9 months) and BrdU+/DCX+ neuroblasts and/or immature neurons (-83% at 12 months) declined the most, whereas proliferating Sox1+ NPCs only dropped by 53%. Remarkably, despite greatly reduced proliferative rates and recent reports of Nestin+ neuroprogenitor loss, total numbers of early Sox1+ NPCs were unaffected by age (at least up to middle age), and newborn cell survival within the dentate gyrus was increased. Neuronal differentiation was concomitantly reduced; however, thus suggesting age-associated changes in fate-choice determination.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Sjoukje D
authors.initials: SD
authors.lastname: Kuipers
authors.affiliation: SBV-Management, Hochheim aM, Germany.
authors.forename: Joern E
authors.initials: JE
authors.lastname: Schroeder
authors.affiliation: Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; Department of Molecular Neurobiology, Centre for Behaviour and Neurosciences, University of Groningen, Groningen, the Netherlands. Electronic address: atrentani@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Trentani
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D018891:Dentate Gyrus / Q000166:cytology; D000089662:Doublecortin Protein; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; C107475:Esx1 protein, mouse; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
keywords: Aging; BrdU; Dentate gyrus; Doublecortin; Granule cell layer; Nestin; Neurogenesis; Neuroprogenitor cells; Sox1; Subgranular zone