Social Experience and Adult Neurogenesis

描述（由申请人提供）：在许多哺乳动物物种中， 已经发现齿状回的神经发生在整个成年期持续 海马回（DG）和脑室下区（SVZ）。新增殖 在大脑的其他区域也发现了这种细胞，包括杏仁核和 下丘脑尽管已经发现有多种因素影响成人 神经发生，潜在的机制仍有待确定。我有 最近发现，暴露于交配48小时的雄性， 增加成年雌性草原动物DG、SVZ和杏仁核的神经发生 田鼠、褐腹田鼠（Microtus ochrogaster）（16）。由于男性接触会增加 循环雌激素（10，45）和雌激素增强的表达， 脑源性神经营养因子（BDNF）在大脑中（37）在雌性草原 BDNF治疗增强大鼠SVZ的神经发生（33），I 假设雌激素和BDNF相互作用调节成人神经发生 雌性草原田鼠提出了三项研究来检验这一假设， 专注于DG的神经发生。在具体目标1中， 不同的社会环境或不同的荷尔蒙影响下， 检查DG中增殖细胞的数量以检验假设 与男性接触相关的雌激素激增是导致 增加神经发生。在《特定目标2》中，雌性田鼠将接受大脑 输注不同剂量的BDNF以测试BDNF作用于 上调神经发生在具体目标3中，将使用双标记方法 用于检查trkB（BDNF受体）在增殖的 细胞来验证BDNF直接调节神经发生的假设。 总之，这些研究应该提供一个理解， 雌激素和BDNF在神经发生调节中的关系 特别是雌性草原田鼠，并将进一步促进我们的整体 了解成年人的激素和神经机制 神经发生

DESCRIPTION (provided by applicant): In a number of mammalian species, neurogenesis has been found to continue throughout adulthood in the dentate gyrus of the hippocampus (DG) and subventricular zone (SVZ). Newly proliferated cells have also been found in other brain regions, including the amygdala and hypothalamus. Although a variety of factors have been found to influence adult neurogenesis, the underlying mechanisms remain to be determined. I have recently found that exposure to a male with mating for 48 hrs significantly increases neurogenesis in the DG, SVZ, and amygdala of adult female prairie voles, Microtus ochrogaster (16). Since male exposure increases the level of circulating estrogen (10, 45) and estrogen enhances the expression of brain-derived neurotrophic factor (BDNF) in the brain (37) in female prairie voles, and BDNF treatment enhances neurogenesis in the SVZ in rats (33), I hypothesize that estrogen and BDNF interact to regulate neurogenesis in adult female prairie voles. Three studies are proposed to test this hypothesis by focusing on neurogenesis in the DG. In Specific Aim 1, female voles in different social environments or under different hormonal influences will be examined for the number of proliferating cells in the DG to test the hypothesis that the estrogen surge associated with male exposure is responsible for increasiag neurogenesis. In Specific Aim 2, female voles will receive brain infusions of different doses of BDNF to test the hypothesis that BDNF acts to up-regulate neurogenesis. In Specific Aim 3, double labeling methods will be employed to examine the presence of trkB, the BDNF receptor, on proliferated cells to test the hypothesis that BDNF acts directly to regulate neurogenesis. Taken together, these studies should provide an understanding of the relationship between estrogen and BDNF in the regulation of neurogenesis in female prairie voles, in particular, and will further contribute to our overall understanding of the hormonal and neuronal mechanisms underlying adult neurogenesis.