Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation

Neurobiol Aging. 2004 Mar;25(3):361-75. doi: 10.1016/S0197-4580(03)00090-3.


Neurogenesis and apoptosis in the hippocampal dentate gyrus (DG) occur during development and adulthood. However, little is known about how these two processes relate to each other during aging. In this study, we examined apoptosis, proliferation, migration, and survival of newborn cells in the young (2 weeks), young-adult (6 weeks), middle-aged (12 months), and old (24 months) rat DG. We also measured dentate volume and cell numbers, along with basal corticosterone and stress response parameters. We show that new cell proliferation and apoptosis slow down profoundly over this time period. Moreover, migration and differentiation into a neuronal or glial phenotype was strongly reduced from 6 weeks of age onwards; it was hardly present in middle-aged and old rats as confirmed by confocal analysis. Surprisingly, we found no correlation between cell birth and corticosterone levels or stress response parameters in any age group.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Apoptosis / physiology*
  • Biomarkers
  • Cell Count
  • Cell Differentiation / physiology*
  • Cell Division / physiology
  • Cell Movement / physiology
  • Cell Survival / physiology
  • Corticosterone / metabolism
  • Dentate Gyrus / cytology
  • Dentate Gyrus / growth & development*
  • Dentate Gyrus / physiology
  • Hypothalamo-Hypophyseal System / metabolism*
  • Male
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / cytology
  • Neuroglia / physiology
  • Neurons / cytology
  • Neurons / physiology
  • Phenotype
  • Pituitary-Adrenal System / metabolism*
  • Rats
  • Rats, Wistar
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Stress, Physiological / metabolism


  • Biomarkers
  • Nerve Tissue Proteins
  • Corticosterone