Mitogen and stress-activated protein kinase (MSK1/2) regulates ischemia-induced neurogenesis and morphological maturation

The 18th Denman Undergraduate Research Forum Secound Place in Biological SciencesPathophysiological conditions such as cerebral ischemia (stroke) trigger the production of new neurons in the hippocampus dentate gyrus. The functional significance of ischemia-induced neurogenesis is believed to be the regeneration of lost cells, thus contributing to post-stroke recovery. However, the cellular signaling mechanisms by which this process is regulated are still under investigation. Recent data from our lab indicate a role for mitogen and stress-activated protein kinases (MSK1/2) in the regulation of hippocampal progenitor cell proliferation after repeated seizure insult. In the present study we tested the hypothesis that MSK1/2 signaling is a regulator of ischemia-induced neurogenesis and neuronal morphological maturation. To test this hypothesis we induced transient ischemia by infusion of the potent vasoconstrictor endothelin-1 into the hippocampus. Following ischemic induction, hippocampal tissue was immunolabeled for bromodeoxyuridine (BrdU, a marker of newly dividing cells) and doublecortin (DCX, a marker for immature neurons). Detailed analysis of the granule cell layer (GCL) of the dentate gyrus indicates delayed maturation of newborn neurons in MSK1/2 null mice compared to wild type (WT) controls. Further, we performed a structural analysis of BrdU-tagged neurons born after ischemia in order to evaluate the maturation of the newly generated neurons, as a measurement of function capability. Taken together, these data suggest that MSK1/2 plays a significant role in the regulation of ischemia-induced neurogenesis and we will further investigate the morphological maturation of the newborn neurons.No embargoAcademic Major: Pharmaceutical Science