Our long-term goal is to identify the neurochemical mechanisms that are associated with the functional-morphological changes responsible for observed decrements in physiological function with aging. Adrenergic transmitters, neuropeptide Y (NPY), and angiogenic II (ANG II) cause hypertension, increase ingestive behavior, inhibit sexual function, modify pituitary hormone section (for gonadotropin secretion the nature of the modification [stimulatory or inhibitory] is determined by the prevailing sex steroid milieu), modify activity and affect, and regulate energy balance. In brain, and sympathetic neurons (and the adrenal medulla), NPY is extensively co-localized with adrenergic transmitters. Further, ANG II potential the release of adrenergic transmitters and NPY from adrenergic transmitters. We proposed that dynamic changes in the hormonal milieu influence age- and experience-related changes in adrenergic-neuropeptide interactions. More specifically, we suggest that age-related changes in function/gene expression of alpha-2-adrenergic, NPY and ANG II receptors are major contributors to the age-related decrements in cardiovascular, sexual, and cognitive function.
Our Specific Aims are to test the following hypotheses: [1] alpha-2- adrenergic, Y1, Y5, and AT1a receptors exhibit dynamic changes in function with aging. The nature and extent of these functional changes is determined by the preceding sex steroid exposure and behavioral history of the individual. Further, the nature and extent of these changes dictate the degree of age-related alterations in cardiovascular, sexual, and cognitive function; [2]. The regulation of alpha 2 adrenergic, Y1, Y5, and AT1a receptor function/gene expression is modified by hormonal by hormonal deprivation/replacement. Specifically, androgen deprivation modifies receptor function/gene expression in a neural site- selective/specific manner. Further, varying the length of the hormonal hiatus, as well as the age at which it occurs, differentially affects physiological and behavioral, as well as adrenergic/neuropeptide, function. These studies will establish the """"""""normal"""""""" patterns of age-related changes in blood pressure, sexuality, and cognition in individual male rats, which will be correlated to changes in adrenergic transmitter, NPY, and ANG II function. The results will provide a unique contribution to understanding of age-associated alterations in adrenergic-neuropeptide interactions (and how they are modified by gonadal hormones) in the regulation of physiological function and behavior. The data will allow for a clear separation of the effects of age per se, behavioral experience and hormonal deprivation/replacement, with specific correlations to neural site-specific/selective changes in adrenergic, NPY, and ANG II receptor function/gene expression.
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