Mechanisms and therapeutic implication of survival of newborn neurons in the ischemic hippocampus

Abstract

Brain ischemia stimulates neurogenesis. Previous studies have focused on proliferation of neural stem cells. However, newborn neurons show a progressive decrease in number over time. First, we have shown that apoptosis could be involved in decrease of newborn neurons by TUNEL staining and Bcl-2 transgenic mouse. Then, we examined the involvement of cAMP responsive element binding protein (CREB) and CRE-mediated pathway in the survival of newborn neurons. Newborn neurons shows strongly positive signal for CREB phosphorylation. When we inhibited CRE-mediated gene expression, the number of newborn neurons decreased. In contrast, survival of newborn neurons was enhanced by administration of rolipram, inhibitor of phosphodiesterase IV, which could increase the level of cAMP. Our findings demonstrated the potential value of strategy for enhancing survival of newborn neurons after ischemia.