PILOT PROJECT--GENE REGULATION IN VASOPRESSIN NEURONS DURING AGING

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The objective of this research program is to determine the effect of aging on gene expression in vasopressin (VP) neurons. We have demonstrated that the VP response to chronic dehydration is attenuated in aged rats. Aged rats have a decreased concentration of VP in the neural lobe, and VP synthesis is decreased in aged rats. In addition, in patients with Alzheimer's disease, VP is decreased in the cerebrospinal fluid, and abnormalities exist in VP release from the neural lobe. These observations suggest that the function of VP neurons may be compromised in aging and Alzheimer's disease. Several laboratories have demonstrated that VP mRNA levels increase in the supraoptic (SON) and paraventricular nuclei (PVN) during chronic salt loading, and recently investigations have demonstrated that the nuclear protein, fos, is rapidly expressed in supraoptic neurons in response to dehydration or an acute increase in plasma osmolality. Therefore, we propose to examine the effect of stimuli which increase VP secretion from the neural lobe on Fos, fos mRNA and VPmRNA content in the SON and PVN during aging in order to determine if the system's ability to increase VP secretion in response to chronic stimulation is compromised. Also, we propose to evaluate the effect of aging on VPmRNA content of other VP neurons which participate in regulation of memory processes. The specific aims of this proposal are: 1. To determine the effect on aging on VP mRNA content and induction of fos in the supraoptic and paraventricular nuclei in response to chronic dehydration. 2. To determine the effect of aging on induction of fos in the supraoptic and paraventricular nuclei in response to acute increases in osmolality of the extracellular fluid. 3. To determine the effect of aging on VP and VP mRNA content of other nuclei which contain VP producing neurons. The nuclei which will be evaluated are he suprachiasmatic nucleus, the bed nucleus of the stria terminalis, and the locus coeruleus. These preliminary studies will indicate the feasibility of evaluating the effect of aging on VP neurons using indexes of VP mRNA, fos mRNA and Fos content. If these studies are successful, further evaluation of other stimuli for VP release from the neural lobe as well as stimuli which activate the non-neurohypophyseal VP neurons would be appropriate.