Characterizing the effects of aging and traumatic brain injury on the subventricular zone proteome

The recent observation that multipotent neural stem cells persist throughout life in selected regions of the mammalian brain has sparked much interest into the possible functions of these cell types and the feasibility of exploiting their regenerative capacity for therapeutic purposes. Because neural stem/progenitor cells (NSC/NPCs) represent a potential endogenous source for cell replacement, a considerable amount of research has focused on establishing therapies aimed at harnessing, and even further enhancing, their neurogenic capacity to repopulate damaged regions in the brain. The therapeutic implication of NSC/NPCs is of particular interest with regard to neuronal death that results from injury or disease as well as the neurodegenerative processes that occur with aging. Accordingly, the current study aims to determine the extent to which endogenous NSC/NPCs residing in the subventricular zone (SVZ) respond to (1) the normal aging process and (2) traumatic brain injury (TBI). Furthermore, proteomic techniques have been utilized to correlate alterations in SVZ protein expression profiles with age-related or injury-induced changes in the proliferative activity of NSC/NPCs residing in this neurogenic region. Consequently, we have begun to compile a list of candidate proteins that likely contribute to the enhanced proliferation of NSC/NPCs induced by TBI as well as the declines in mitotic behavior that are observed with aging. To further facilitate our understanding of the functional role of neural stem/progenitor cells in the injured or aging brain, new tools must be generated that enable these cells to be distinguished from other CNS cell types. Accordingly, in an additional series of experiments described in this dissertation we introduce a novel experimental paradigm which combines the techniques of x-irradiation, 2D gel electrophoresis and mass spectrometry to elucidate the repertoire of proteins expressed by subventricular NSC/NPCs in vivo. Collectively, these studies contribute to a clearer understanding of the proteins that likely play regulatory roles in the behavior of neural stem/progenitor cells.