Exp Mol Med.  2006 Feb;38(1):44-54.

Chronic mild stress decreases survival, but not proliferation, of new-born cells in adult rat hippocampus

  • 1Department of Pharmacology, Korea University College of Medicine, Seoul 136-705, Korea. kyungho@korea.ac.kr
  • 2Graduate School of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Korea.
  • 3Department of Psychiatry, Korea University College of Medicine, Seoul 136-705, Korea.


New-born cells continue to proliferate and survive to become mature granule cells in adult rat hippocampus. Although this process, known as neurogenesis, is inhibited by acute stress, it is not clear whether chronic stress affects neurogenesis. To determine whether chronic mild stress (CMS) influences neurogenesis in the adult rat hippocampus, male Sprague-Dawley rats were exposed to CMS and administered bromodeoxyuridine (BrdU) before or after CMS to observe the survival/differentiation or proliferation of new-born cells, respectively. In addition, we measured brain-derived neurotrophic factor (BDNF) mRNA in the granule cell layer (GCL) of the hippocampus, because BDNF is known to play an important role in the survival of new-born cells. CMS significantly decreased the survival of newborn cells in the GCL, but did not influence the proliferation or differentiation of new-born cells. CMS did not affect the proliferation and survival of new-born cells in the hilus. In addition, CMS did not change BDNF mRNA levels in the GCL. These results demonstrate that CMS reduces the survival of new-born cells but not of their proliferation, suggesting that repeated mild stress could influence a part of neurogenesis, but not the whole part of neurogenesis. These results raise the possibility that the survival of new-born cells may be suppressed in the presence of normal BDNF mRNA levels in GCL.


brain-derived neurotrophic factor; bromodeoxyuridine; depression; hippocampus; neurogenesis; stress

MeSH Terms

Brain-Derived Neurotrophic Factor/metabolism
Bromodeoxyuridine/*administration & dosage
Calcium-Binding Protein, Vitamin D-Dependent/metabolism
Cell Proliferation
Cell Survival
Comparative Study
Fluorescent Antibody Technique, Indirect
Fluorescent Dyes
Glial Fibrillary Acidic Protein/metabolism
Hippocampus/cytology/growth & development/*pathology
In Situ Hybridization
Microscopy, Confocal
RNA, Messenger/metabolism
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Restraint, Physical
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