The overall goal of this proposal is to understand more about the physiology of galanin-like peptide (GALP) neurons, and particularly within the context of diabetes. The primary aims are 1) to determine the anatomical organization of GALP neurons with respect to other known neuroendocrine mediators of reproduciton and feeding and to learn wether this circuitry is altered in the diabetic state; and 2) to explore the role of GALP in mediating the effects of leptin and insulin on the reproductive system, by examining the effects of centrally administered GALP on the reproductive axis and behaviors in a rodent model of type I diabetes. All experimental manipulations will be carried out in the diabetic male rat and compared to normal controls. Diabetic status will induced pharmacologically with subcutaneous injections of streptozotocin at a dose known to induce diabetes in at least 95% of animals without altering glucocorticoid levels. Control animals will be injected withvehicle. To accomplish these goals, the use of various neuroanatomical techniques, including retrograde tract-tracing combined with single- and double-label immunocytochemistry, will be used to map the hypothalamic circuitry linking GALP to other neurotransmitter systems in the hypothalamus. Analysis of male-specific sex behaivors following intracerebral injections of GALP and/or galanin will provide evidence for the role of these neuropeptides in the regulation of reproductive behaivors. Furthermorequantitative in sity hybridization will be used to determine the effects of hormonal and behavioral manipulations on GALP mRNA within the hypothalamus. It is hoped that this basic knowledge will lead to a better understanding of disorders of reproduction that are associated with diabetes and thus provide an enlightened path towards their treatment.
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