| Popis: |
Many lines of recent studies have demonstrated that endogenous neural stem/progenitor cells (NPCs) contribute to the production of new neurons in selected brain regions following ischemic injury. In other regions, such as the neocortex, regeneration appears to be limited. Previous work in the Nakafuku Lab demonstrated that the migration, survival, and/or differentiation of NPCs from the pPV to the damaged cortical gray matter is restricted. I hypothesized that environmental cues differentially regulate the behavior of NPCs between the adjacent cortex and hippocampus, in which neurogenesis occurs. In order to better characterize the events underlying this restriction of regeneration, I used a rat model of transient forebrain ischemia, in which NPCs resident in the posterior periventricular region (pPV) regenerate hippocampal CA1 pyramidal neurons lost after injury, whereas few new neurons are regenerated in the neocortex. To explore the nature of such environmental cues, I performed microarray analysis for comprehensive gene expression profiling of ischemic brains. These studies identified multiple genes that showed differential expression patterns between the cortex and hippocampus at the time when neurogenesis occurs in the hippocampus. Notably among them were genes encoding insulin-like growth factor (IGF)-I and its regulators, which were highly expressed in the hippocampus, but not the cortex. Administering IGF-I in the cortex of adult ischemic rats, stimulated NPCs in the pPV and increased the number of newborn neurons in the neocortex. These results suggest that IGF-I promotes neurogenesis after ischemia in a region where neurogenesis is otherwise restricted. |
