OLFACTORY DEGENERATION--A MODEL

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In order to understand aging of the brain in man and the neurodegeneration associated with aging such as Alzheimer's disease, it has become increasingly evident that a broad understanding of aging mechanisms must be obtained by studies of a wide spectrum of vertebrates. Such data from these animal models will likely define both generalized and specialized aspects of aging in the olfactory system as well as providing insights into molecular factors which affect degenerative processes. We propose to employ a new exciting model for olfactory aging research, namely salmon. The proposed studies are prompted by our finding that: 1) our antibodies to the carboxyl terminal of the Alzheimer amyloid precursor protein (APP) recognize membrane associated proteins in salmon brain, 2) anti-APP (Boehringer-Mannheim) recognizes salmon brain proteins, 3) coho salmon cultured on a restricted diet do not die at the age of three years but are still alive at the age of five years. 4) Cultures of olfactory cells have been reported as model systems for studying cytokines and growth factors as well as potentiators, such as melatonin, and 5) an Institute of Arctic Biology researcher has demonstrated that in vivo dialysis can be carried out on salmon. We, therefore, propose to study normal 3-year-old homeward migrants a well as cultured salmon at 3 and 5 years of age with respect to the roles of proteins in morphological changes during rapid aging. The following parameters will be determined in these populations: 1) quantity and distribution of APP, 2) quantity of various growth factors and their receptors during migration using immunochemistry and quantitative receptor autoradiography, and 3) dendritic morphological changes with the Golgi method. We will develop a cell culture system for salmon olfactory cells, as well as design in vivo experiments. Dr. Gerhardt has extensive experience in using in vivo methods to investigate change in neurochemicals such as serotonin, melatonin, dopamine, and norepinephrine. e will direct my training in the areas of neurochemistry and neuropharmacology as applied to the development of a salmon model for the olfactory system. Also, a long-term goal would be to develop some human clinical research on olfactory aging in a high latitude population such as Fairbanks.