The presence of adult neural stem and progenitor cells in the mammalian brain has awakened new interest and optimism in potential treatment for a variety of acquired brain disorders. It is, however, unclear what role, if any, adult neural stem cells play in contributing to post-injury recovery. We are interested in defining how adult neural stem and progenitor cells participate in injury-induced remodeling and in identifying genes that might be important in augmenting their contribution. The hippocampus is central to the formation of memory and has recently been implicated in higher cognitive functioning as well. In all mammals, the one area of the hippocampus that has constant neuronal turnover due to a persistent population of neural stem and progenitor cells is the dentate gyrus. The dentate gyrus functions to integrate cortical input and transmit this to other areas of the hippocampus. We study how the dentate gyrus develops and responds to injury such as trauma and hypoxia at varying ages. In order to do this, we have taken a genetic approach in mice that allows us to trace stem and progenitor cells within the hippocampus and gives us the ability to perform temporally specified genetic changes. We have developed a variety of tools to do this including tetracycline, tamoxifen, and ganciclovir-based systems that allow for fate labeling, progenitor ablation, and temporally and spatially regulated genetic deletions. Moreover, the addition of fluorescent tags in these transgenics allows us to quantify the number of adult neural stem cells during development and activated by injury by utilizing fluorescent activated cell sorting (FACS). These models make up the foundation to our lab’s approach of understanding how neural stem and progenitor cells may contribute to recovery following acquired brain injury.
Gilley, J.A., Yang, C.P., and Kernie, S.G.
Developmental profiling of postnatal dentate gyrus progenitors provides evidence for dynamic cell-autonomous regulation. Hippocampus. 21(1): 33-47.. (2011)
Blaiss, C.A., Yu, T.S., Zhang, G., Chen, J., Dimchev, G., Parada, L.F., Powell, C.M., and Kernie, S.G.
Temporally specified genetic ablation of neurogenesis impairs cognitive recovery following traumatic brain injury. Journal of Neuroscience. 31(13): 4906-4916.. (2011)
Yang, C.P., Gilley, J.A., Zhang, G. and Kernie, S.G.
ApoE is required for maintenance of the dentate gyrus neural progenitor pool. Development. 138(20):4351-4362.. (2011)
Gilley, J.A. and Kernie, S.G.
GltI and Glast negatively regulate calcium-dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury European Journal of Neuroscience. 34(11): 1712-1723.. (2011)
Yu, T.S., Zhang, G., Liebl, D.J., and Kernie, S.G.
Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors. Journal of Neuroscience. 28(48):12901-12912. (2008)