Social Experience and Adult Neurogenesis

描述(申请人提供)：在许多哺乳动物物种中， 已发现齿状体内的神经发生持续到成年期。 海马区(DG)和脑室下区(SVZ)。新扩散的 在其他大脑区域也发现了细胞，包括杏仁核和 下丘脑。尽管已发现多种因素会影响成人 神经发生，其潜在的机制仍有待确定。我有过 最近发现，与交配了48小时的雄性接触显著 增加成年雌性草原DG、SVZ和杏仁核的神经发生 田鼠(Microtus Ochrogaster)(16)。因为男性接触会增加体内的 循环雌激素(10，45)和雌激素促进血管内皮生长因子表达 草原雌性动物脑组织中脑源性神经营养因子的含量(37) 和BDNF治疗促进了大鼠SVZ的神经发生(33)，即 雌激素和脑源性神经营养因子相互作用调节成人神经发生的假说 雌性草原田鼠。为了验证这一假设，有三项研究被提出 重点放在DG的神经发生上。在特定目标1中，雌性田鼠进入 不同的社会环境或在不同的荷尔蒙影响下 检查DG中增殖细胞的数量以检验这一假设 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，雌性田鼠将获得大脑 不同剂量的脑源性神经营养因子对脑源性神经营养因子作用于 上调神经发生。在具体目标3中，双重标记方法将是 用来检测增殖的BDNF受体TrkB的存在 细胞来测试BDNF直接作用于调节神经发生的假设。 综上所述，这些研究应该会提供对 雌激素与脑源性神经营养因子在神经发生调控中的关系 尤其是雌性草原田鼠，并将进一步为我们的整体 理解成体背后的激素和神经机制 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.