The Role of PKCδII in Insulin-Mediated Neurogenesis

Protein Kinase C delta (PKCδ) is a Serine/Threonine signaling kinase involved in a number of different cellular functions including cell differentiation, proliferation, and apoptosis. PKCδ improves learning and memory by preventing neuronal loss and maintaining the synapses. Data from our lab demonstrates that insulin regulates the alternative splicing of PKCδ pre-mRNA and promotes the expression of PKCδII, the splice variant that promotes neuronal survival. PKCδI, another splice variant of PKCδ, causes apoptosis of neurons. Our preliminary data and previous studies demonstrate that intranasal insulin improves cognitive ability in mice. The goal is now to determine the downstream components through which insulin is able to accomplish this task. Based on our data, it is hypothesized that insulin acts through PKCδII to increase the expression of other survival proteins in a cascade effect to improve cognition. What now needs to be determined is whether or not the increased levels of PKCδII will in fact increase the levels of the pro-survival genes Bcl2 and Bcl-xL, promoting neuronal survival and thereby increasing cognition. We expect that insulin treatments will increase the expression of PKCδII, Bcl2, and Bcl-xL. We propose that PKCδII is the crucial mediator of the insulin signaling pathway and directly increases the expression of Bcl2 and Bcl-xL