STRESS & AGING ON THE NEUROPEPTIDES IN PERIPHERAL SENSORY AUTONOMIC SYSTEM

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This proposal will test the hypothesis that aging will alter the rate of synthesis and transport of two neuropeptides, substance P and somatostatin, away from sensory ganglia, and that stress will exacerbate this effect. Dr. MacLean has developed a method for measuring the accumulation of these peptides after ligation or local application of colchicine and has begun to assess the influence of anesthetics and nerve manipulation (by capsaicin or VMH lesions) on transport. The first phase of the project will involve examination of acute stress and its effects on peptide content in the vagus nerve, sciatic nerve and sympathetic ganglis in animals that are young (4 mos. - Y), middle aged (11 mos. - M) or old (18 mos. - 0). Ether and shock avoidance stress will be used. In the second experiment, chronic stress (shock avoidance 5 days/week for 7 months followed by a 1 month recovery period) will be applied to animals beginning at 4, 11 or 18 months of age and changes in peptide content will be measures. In the third experiment, animals begun at 11 months (M) will be used to study the effects of stress in the periods up to 7 months in order to get a full time course of the anticipated effects. In the second phase of study, examination of the alterations in transport of somatostatin and substance will be made to evaluate the significance of the altered content. Animals 4, 11, 18 and 24 months of age will be used. Animals in the M group will be used to determine the effects of chronic stress on transport and correlated with content studies from the first phase. M animals (controls and chronically stressed) will be used to measure the neurogenic inflammatory response in the hindpaw as well as alterations in plasma extravasation in response to graded injections of substance P.