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

TLDR

In adult rat hippocampus, newborn cells proliferate and survive to become mature granule cells, a process called neurogenesis that is inhibited by acute stress but whose response to chronic stress is unclear. The study aimed to assess whether chronic mild stress affects neurogenesis in adult rat hippocampus by measuring survival, differentiation, and proliferation of newborn cells using BrdU labeling. Male Sprague‑Dawley rats underwent CMS and received BrdU before or after stress to track newborn cells, while BDNF mRNA levels were measured in the granule cell layer to evaluate its role in cell survival. CMS markedly reduced survival of newborn cells in the granule cell layer without affecting their proliferation or differentiation, had no impact in the hilus, and did not alter BDNF mRNA, indicating that chronic mild stress selectively impairs a subset of neurogenesis while BDNF levels remain unchanged.

Abstract

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.