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.
| Fowler, Christie D; Liu, Yan; Wang, Zuoxin (2008) Estrogen and adult neurogenesis in the amygdala and hypothalamus. Brain Res Rev 57:342-51 |
| Fowler, Christie D; Johnson, Frank; Wang, Zuoxin (2005) Estrogen regulation of cell proliferation and distribution of estrogen receptor-alpha in the brains of adult female prairie and meadow voles. J Comp Neurol 489:166-79 |
| Fowler, Christie D; Freeman, Marc E; Wang, Zuoxin (2003) Newly proliferated cells in the adult male amygdala are affected by gonadal steroid hormones. J Neurobiol 57:257-69 |
