title: Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells.
abstract: Although neural stem cells (NSCs) sustain continuous neurogenesis throughout the adult lifespan of mammals, they progressively exhibit proliferation defects that contribute to a sharp reduction in subventricular neurogenesis during aging. However, little is known regarding the early age-related events in neurogenic niches. Using a fluorescence-activated cell sorting technique that allows for the prospective purification of the main neurogenic populations from the subventricular zone (SVZ), we demonstrated an early decline in adult neurogenesis with a dramatic loss of progenitor cells in 4 month-old young adult mice. Whereas the activated and quiescent NSC pools remained stable up to 12 months, the proliferative status of activated NSCs was already altered by 6 months, with an overall extension of the cell cycle resulting from a specific lengthening of G1. Whole genome analysis of activated NSCs from 2- and 6-month-old mice further revealed distinct transcriptomic and molecular signatures, as well as a modulation of the TGFβ signalling pathway. Our microarray study constitutes a cogent identification of new molecular players and signalling pathways regulating adult neurogenesis and its early modifications.
authors.affiliation: CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, UMR 967, F-92265 Fontenay-aux-Roses, France.|INSERM, UMR967, F-92265 Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, F-92265 Fontenay-aux-Roses, France.|Université Paris Sud, UMR 967, F-92265 Fontenay-aux-Roses, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Daynac
authors.affiliation: CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, UMR 967, F-92265 Fontenay-aux-Roses, France.|INSERM, UMR967, F-92265 Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, F-92265 Fontenay-aux-Roses, France.|Université Paris Sud, UMR 967, F-92265 Fontenay-aux-Roses, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Morizur
authors.affiliation: CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, UMR 967, F-92265 Fontenay-aux-Roses, France.|INSERM, UMR967, F-92265 Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, F-92265 Fontenay-aux-Roses, France.|Université Paris Sud, UMR 967, F-92265 Fontenay-aux-Roses, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chicheportiche
authors.affiliation: CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, UMR 967, F-92265 Fontenay-aux-Roses, France.|INSERM, UMR967, F-92265 Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, F-92265 Fontenay-aux-Roses, France.|Université Paris Sud, UMR 967, F-92265 Fontenay-aux-Roses, France.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Mouthon
authors.affiliation: CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, UMR 967, F-92265 Fontenay-aux-Roses, France.|INSERM, UMR967, F-92265 Fontenay-aux-Roses, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR 967, F-92265 Fontenay-aux-Roses, France.|Université Paris Sud, UMR 967, F-92265 Fontenay-aux-Roses, France.
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D015415:Biomarkers; D002452:Cell Count; D002453:Cell Cycle; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D020547:Lateral Ventricles / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis
chemical_list: D015415:Biomarkers