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 new-born 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.
Highlights
The adult mammalian brain is capable of neurogenesis throughout life, but this is restricted to two major regions in brain: the olfactory bulb and the hippocampus (Cameron et al, 1994; Gould et al, 2002)
The results of the present study demonstrate that chronic mild stress (CMS) reduces the survival of new-born cells in the granule cell layer (GCL) and dentate gyrus of the adult rat hippocampus
In contrast to the reduced survival of new-born cells in the GCL in response to CMS, no difference in proliferation of new-born cells was seen between control and CMS-exposed rats, suggesting that CMS selectively suppress the survival of new-born cells in the hippocampus, but not their proliferation
Summary
The adult mammalian brain is capable of neurogenesis throughout life, but this is restricted to two major regions in brain: the olfactory bulb and the hippocampus (Cameron et al, 1994; Gould et al, 2002). It has been demonstrated that stress reduces new-born cell proliferation in the hippocampus (Gould et al, 1997; Tanapat et al, 1998), whereas treatment with chronic antidepressants increases proliferation (Malberg et al, 2000; Duman et al, 2001). As a result, repeated stress may contribute to the reduction in hippocampal volume reported in patients with depression (Bremner et al, 2000) in part through reduced neurogenesis in the hippocampus, which could be prevented by chronic antidepressant treatment (Czeh et al, 2001; Li et al, 2004). Several factors play a role in the regulation of neurogenesis, and in particular, neurotrophic factors are known to be critical for the survival of new-born cells during their development in vivo and in culture (Palmer et al, 1997). Singing behavior has been reported to increase the expression of BDNF, and this was found to be correlated with the extent of new Monday
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