Project 171464

Successful treatment of neurodegenerative disease must involve therapy designed not only to limit the extent of brain cell destruction but also to stimulate repopulation of damaged tissue. Cell-replacement strategies are key to achieving this goal. The mammalian adult brain, once thought to be completely post-mitotic, is now recognized to contain a finite number of neural stem and progenitor cells with the capacity for self-renewal and the ability to differentiate into functional brain cells. To realize the therapeutic potential of these cells, endogenous stem cells must be able to survive in injured tissue, respond to proliferative cues released by damaged brain, and yet cease division, once normal cell number and cell circuitry has been attained. Our research is designed to study functional brain repair in degenerating tissue by developing a clearer understanding of how environmental changes impact upon the survival of stem cells over the lifespan of an organism. Specifically, by using a unique combination of phytochemical (plant chemistry), genetic (mouse models of human disease), and molecular approaches in cells and and animals, we aim to show: (a) that changing how stem cells communicate with adjacent cells in adult brain can be used to enhance brain repair. (b) that compounds found in specific plants can be identified and used to target this type of communication and accelerate functional cell replacement in injured brain. Our research will provide new insight into how the diseased microenvironment regulates the integration of neural stem and progenitor cells into damaged circuits while leading to the development of new reagents that test the effectiveness of this "medicine from food" strategy as an adjuvant treatment for neurodegenerative disease.

targeting connexins to promote functional neuroregeneration using phytochemical and genetic approaches