- Browse by Subject
Browsing by Subject "neural stem/progenitor cells"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Enhancing Neurogenesis in the Aging Brain through mTOR Pathway Activation(Office of the Vice Chancellor for Research, 2013-04-05) Romine, Jennifer; Gao, XiangThe 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 signaling related to age-related decline in neurogenesis. We found that the total number of NSCs, including quiescent neural progenitors (QNPs) and amplifying neural progenitors (ANPs) decreased as the mice aged, but more importantly, 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 proliferation in aged mice. In contrast, inhibiting the activity of the mTOR signaling pathway by rapamycin is sufficient to reduce ANP proliferation in young mice. These results indicate that NSCs become 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. Following stimulation of the mTOR signaling pathway with Ketamine, we found a significant increase in the number of mature neurons. In order to determine whether or not a further increase in hippocampal neurogenesis is possible, we will next examine the ratio of newborn neuron survival.Item Traumatic Brain Injury Stimulates Neural Stem Cell Proliferation via Mammalian Target of Rapamycin Signaling Pathway Activation(Society for Neuroscience, 2016-09) Wang, Xiaoting; Seekaew, Pich; Gao, Xiang; Chen, Jinhui; Department of Neurological Surgery, School of MedicineNeural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2'-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI.