title: Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus.
abstract: Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results indicate that adult hippocampal stem cells, upon exiting their quiescent state, rapidly undergo a series of asymmetric divisions to produce dividing progeny destined to become neurons and subsequently convert into mature astrocytes. Thus, the decrease in the number of neural stem cells is a division-coupled process and is directly related to their production of new neurons. We present a scheme of the neurogenesis cascade in the adult hippocampus that includes a proposed "disposable stem cell" model and accounts for the disappearance of hippocampal neural stem cells, the appearance of new astrocytes, and the age-related decline in the production of new neurons.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Encinas
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Michurina
authors.forename: Natalia
authors.initials: N
authors.lastname: Peunova
authors.forename: June-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Julie
authors.initials: J
authors.lastname: Tordo
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Peterson
authors.forename: Gord
authors.initials: G
authors.lastname: Fishell
authors.forename: Alex
authors.initials: A
authors.lastname: Koulakov
authors.forename: Grigori
authors.initials: G
authors.lastname: Enikolopov
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D019295:Computational Biology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D055153:Stem Cell Niche
chemical_list: D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D049452:Green Fluorescent Proteins