Presentation Type
Poster
The Role of PKCδII in Insulin-Mediated Neurogenesis
Abstract
Protein Kinase C delta (PKCδ) is a serine/threonine kinase which plays an important role learning and memory. 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. Further, intranasal treatment of insulin increases cognition in older mice. Our preliminary data and previous studies lead us to hypothesize that insulin mediates its cognitive effects through the pro-survival protein PKCδII to increase neuronal survival. It is hypothesized that insulin acts through PKCδII to increase the expression of the survival proteins Bcl-2 and Bcl-xL, which are known to improve neurogenesis and increase neuronal survival. To test this, we treated primary neuronal cells derived from the hippocampus of adult mice with increasing doses of insulin. In separate experiments, we transiently transfected PKCδII-pTracer plasmids to over-express PKCδII and performed RT-PCR and western blot analysis. We demonstrate that insulin increases Bcl2 and Bcl-xL expression via PKCδII. Our results suggest that PKCδII is the crucial mediator of the insulin signaling pathway and promotes memory and cognition via expression of Bcl2 and Bcl-xL.
Categories
Biomedical Sciences
Research Type
Thesis
Mentor Information
Dr. Niketa Patel
The Role of PKCδII in Insulin-Mediated Neurogenesis
Protein Kinase C delta (PKCδ) is a serine/threonine kinase which plays an important role learning and memory. 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. Further, intranasal treatment of insulin increases cognition in older mice. Our preliminary data and previous studies lead us to hypothesize that insulin mediates its cognitive effects through the pro-survival protein PKCδII to increase neuronal survival. It is hypothesized that insulin acts through PKCδII to increase the expression of the survival proteins Bcl-2 and Bcl-xL, which are known to improve neurogenesis and increase neuronal survival. To test this, we treated primary neuronal cells derived from the hippocampus of adult mice with increasing doses of insulin. In separate experiments, we transiently transfected PKCδII-pTracer plasmids to over-express PKCδII and performed RT-PCR and western blot analysis. We demonstrate that insulin increases Bcl2 and Bcl-xL expression via PKCδII. Our results suggest that PKCδII is the crucial mediator of the insulin signaling pathway and promotes memory and cognition via expression of Bcl2 and Bcl-xL.
