Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus

Juan M. Encinas, Tatyana V. Michurina, Natalia Peunova, June Hee Park, Julie Tordo, Daniel A. Peterson, Gord Fishell, Alex Koulakov, Grigori Enikolopov

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)566-579
Number of pages14
JournalCell Stem Cell
Volume8
Issue number5
DOIs
StatePublished - May 6 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Encinas, J. M., Michurina, T. V., Peunova, N., Park, J. H., Tordo, J., Peterson, D. A., Fishell, G., Koulakov, A., & Enikolopov, G. (2011). Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell, 8(5), 566-579. https://doi.org/10.1016/j.stem.2011.03.010