Lee Kuem-Ju, Kim Sung-Jin, Kim Suk-Won, Choi Song-Hyen, Shin You-Chan, Park Sang-Ha, Moon Bo-Hyun, Cho Eujin, Lee Min-Soo, Choi Sang-Hyun, Chun Boe-Gwun, Shin Kyung-Ho
Graduate School of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Korea.
Exp Mol Med. 2006 Feb 28;38(1):44-54. doi: 10.1038/emm.2006.6.
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.
新生细胞持续增殖并存活，最终在成年大鼠海马体中成为成熟的颗粒细胞。尽管这一过程，即所谓的神经发生，会受到急性应激的抑制，但慢性应激是否会影响神经发生尚不清楚。为了确定慢性轻度应激（CMS）是否会影响成年大鼠海马体中的神经发生，将雄性Sprague-Dawley大鼠暴露于CMS环境中，并在CMS之前或之后给予溴脱氧尿苷（BrdU），以分别观察新生细胞的存活/分化或增殖情况。此外，我们测量了海马体颗粒细胞层（GCL）中的脑源性神经营养因子（BDNF）mRNA水平，因为已知BDNF在新生细胞的存活中起重要作用。CMS显著降低了GCL中新生细胞的存活率，但不影响新生细胞的增殖或分化。CMS对门区新生细胞的增殖和存活没有影响。此外，CMS没有改变GCL中BDNF mRNA的水平。这些结果表明，CMS降低了新生细胞的存活率，但不影响其增殖，这表明反复的轻度应激可能会影响神经发生的一部分，但不是整个神经发生过程。这些结果增加了一种可能性，即在GCL中BDNF mRNA水平正常的情况下，新生细胞的存活可能会受到抑制。
