The purpose of this grant application is to obtain support and necessary training for the development of research skills needed to become a successful, productive independent investigator in the neurobiology of aging in an academic medicine setting. The proposed training is to be divided into two phases to extend over a total of five years. The initial two years (Phase I) will consist of didactic instruction combined with supervised experience in laboratory techniques relevant to the cell biology of the aging nervous system. Laboratory methods will be learned by """"""""hands-on"""""""" experience directly supervised by investigators and technicians already well-versed in them. Such resource people are readily available both within the Department of Neurobiology and Anatomy and the Department of Biology as well as throughout the University of Rochester at large. These methods will include, but not be limited to immunocytochemistry and other morphological approaches, cell culture techniques, gel electrophoresis, immunoblotting and enzyme immunoassay. Special emphasis will be on the aging brain in both normal and disease state. During Phase I of the grant, time will also be spent participating in regularly scheduled seminars on aging sponsored by the University of Rochester NIA sponsored Training Grant in Geriatrics and the Neurobiology of aging and by the Department of Neurobiology and Anatomy. Other available didactic sessions include (1) Neurology Grand Rounds at Strong Memorial Hospital (2) """"""""brain-cutting conferences conducted on a weekly basis by the Division of Neuropathology in conjunction with the University of Rochester Alzheimer's disease (AD) project and (3) scheduled visits to laboratories of active investigators throughout the University of Rochester Medical Center and the adjacent River Campus. Relevant graduate courses given throughout the academic year by the University of Rochester will be taken. Satisfactory completion of Phase I will be determined by the primary sponsor and cosponsor and will be based on the candidate's accumulation of knowledge and research skills. The subsequent three years (Phase II) will be spent applying the skills obtained during Phase I to a defined research project. Initial plans for Phase II involve the study of changes in glial cells with normal aging and in Alzheimer's disease. The role of glia as a source of neurotrophic factors, particularly nerve growth factor, will be determined. A closely related project planned for Phase II is the study of the effect and the mechanism of effect of neurotrophic factors on microtubule associated proteins (MAPs) and on the cytoskeletal structure of the aging neuron. These studies will also be concerned with the study of MAPs as markers for changes in dendritic and glial distribution with normal aging and with Alzheimer's disease.
