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

Cell Stem Cell. 2011 May 6;8(5):566-79. doi: 10.1016/j.stem.2011.03.010.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cell Survival
  • Cognition Disorders / pathology*
  • Cognition Disorders / physiopathology
  • Computational Biology
  • Green Fluorescent Proteins / genetics
  • Hippocampus / pathology*
  • Intermediate Filament Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nestin
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / pathology
  • Stem Cell Niche


  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Green Fluorescent Proteins