The continuation of neurogenesis in certain regions of the adult mammalian brain suggests that these regions may express signals to maintain continued proliferation of neural stem cells with subsequent differentiation of their progeny. Understanding these mechanisms may be useful for the development of therapeutic strategies for structural brain repair. However, neurogenesis declines in the aging hippocampus, suggesting that the signals maintaining neurogenesis may also decline with aging. We have recently determined that neurogenesis is also significantly reduced in the olfactory bulb with aging, despite previous reports that proliferation in the subventricular zone is unaffected by age. As proliferation also occurs in the rostral migratory stream, this project will quantify age-related changes in the rostral migratory stream by confocal stereology using our recently described thymidine analog markers to reveal the proliferative history of cells in subregions of the rostral migratory stream. Equivalent regions will also be sampled by laser microdissection for subsequent quantitative RT-PCR analysis of age-related changes in gene expression for candidate neurogenic signals. The use of stereology will reveal age-related changes in cell number in the regions analyzed for gene expression. This relationship will be used to normalize the gene expression data to actual cell number for greater biological relevance. Data resulting from these studies will advance our knowledge of neural stem cell regulation and may lead to restorative strategies for the age-impaired brain.
