Browsing by Subject "neural stem/progenitor cells (NSCs)"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    OVERCOMING THE AGE-ASSOCIATED DECLINE IN NEURAL STEM CELL PROLIFERATION
    (Office of the Vice Chancellor for Research, 2012-04-13) Romine, Jennifer; Gao, Xiang; Chen, Jinhui
    The U.S. population is aging. Age-related cognitive decline is a major public health problem. Developing an approach to treat or delay cognitive decline is critical. Neurogenesis by neural stem/progenitor cells (NSCs) in the hippocampus is related to cognitive function, and is greatly affected by the aging process. The molecular signaling that regulates age-related decline in neurogenesis is still poorly understood. Here we took the advantage of a transgenic mouse, Nestin-GFP, to assess neurogenesis and molecular signal-ing related to age-related decline in neurogenesis. We found that the total number of NSCs, including quiescent neural progenitors (QNPs) and amplify-ing neural progenitors (ANPs) decreased as the mice aged, but more im-portantly, ANPs are more significantly affected than QNPs, leading to further reduction in number and proliferation of ANPs. We further found that the mTOR signaling pathway is impaired in NSCs as mice age. Activating the mTOR signaling pathway through Ketamine injections increased NSC prolif-eration in aged mice. In contrast, inhibiting the activity of the mTOR signal-ing pathway by rapamycin is sufficient to reduce ANP proliferation in young mice. These results indicate that NSCs becomes more quiescent when the activity of mTOR signaling is compromised in aged mice, and stimulating the activity of mTOR signaling can overcome the age-associated decline in NSC proliferation. This data suggests that promoting stem cell proliferation to en-hance neurogenesis may be a potential approach for attenuating cognitive decline in the aging brain.This work was supported by funding from the Ralph W. and Grace M. Showalter Research Award, Indiana University Biological Research Grant, NIH grants RR025761 and 1R21NS072631-01A, and Undergraduate Research Opportunities Program (UROP).
  • Thumbnail Image
    Item
    TRAUMATIC BRAIN INJURY LEADS TO ABERRANT MIGRATION OF ADULT-BORN NEURONS IN THE HIPPOCAMPUS
    (Office of the Vice Chancellor for Research, 2012-04-13) Ibrahim, Sara; Gao, Xiang; Chen, Jinhui
    Traumatic brain injury (TBI) is the leading cause of death in children and young adults, leading to substantial cognitive impairment, motor dysfunction and epilepsy. There is no effective treatment for these dis-orders. The discovery of neural stem/progenitor cells (NSCs) in the adult brain raises a potentially promising strategy for repairing CNS in-jury.Our previous study showed that TBI promotes NSC proliferation in an attempt to initiate innate repair and/or plasticity mechanisms. However, the spontaneously post-traumatic recovery of hippocampal-related cognitive and memory functions is very limited. Better under-standing of neurogenesis following TBI may provide additional inter-vention to further enhance neurogenesis for successfully repairing the damaged brain following TBI. Although newborn neurons generated from NSCs are continuously added to the brain throughout our life, they must migrate from their birthplace to their appropriate destina-tion to develop into mature neurons. When we tracked the migration of newly generated neurons in the adult hippocampus after TBI, we found that a large percentage of immature neurons migrate pass their normal stopping site at the inner granular cell layer, and misplace in the outer granular cell layer of the hippocampal dentate gyrus. The aberrant migration of adult-born neurons in the hippocampus occurs 3 days after TBI, and lasts for 10 weeks, resulting in a great number of newly generated neurons misplaced in the outer granular layer in the hippocampus. The newborn neurons at the displaced position will not be able to make correct connections with their appropriate targets, and may even make wrong connections with inappropriate nearby tar-gets in the pre-existing neural network. Abnormal migration can cause several diseases including epilepsy. These results suggest that stimu-lation of endogenous adult neural stem cells following TBI might offer new avenues for cell-based therapy. Additional intervention is required to further enhance successful neurogenesis for repairing the damaged brain.