Age-related effects on hippocampal precursor cell subpopulations and neurogenesis

Neurobiol Aging. 2011 Oct;32(10):1906-14. doi: 10.1016/j.neurobiolaging.2009.11.011. Epub 2009 Dec 16.

Abstract

Hippocampal neurogenesis continuously declines in the aging brain but only little is known about age-related alterations in the subgranular zone (SGZ) of the dentate gyrus which accommodates different subpopulations of precursor cells. Here, we examined the age-related effects on total number and proliferation rate of distinct precursor cell populations in the dentate gyrus of 3 and 16 months old transgenic pNestin-GFP mice. Following a single injection of bromodeoxyuridine (BrdU) we observed a significant reduction of all proliferating precursor subtypes in aged mice compared to young controls. Stereological analysis further revealed that this decreased proliferation was not only caused by a general reduction in total number of precursor subtypes but also by a subtype-specific alteration of the proliferation rate. Whereas radial glia-like and early neuronal precursor cells demonstrate decreased proliferation rates, no difference was found for doublecortin-positive precursors. Additional long-term experiments further revealed that these age-related alterations in the proliferative zone were accompanied by a strongly decreased neurogenesis while hippocampal function was not impaired.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Doublecortin Domain Proteins
  • Green Fluorescent Proteins / genetics
  • Hippocampus / cytology*
  • In Situ Nick-End Labeling
  • Indoles
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Learning Curve
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neural Stem Cells / classification*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology*
  • Neurogenesis / physiology*
  • Neuropeptides / metabolism
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Doublecortin Domain Proteins
  • Indoles
  • Intermediate Filament Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Neuropeptides
  • Green Fluorescent Proteins
  • DAPI
  • Bromodeoxyuridine