DESCRIPTION: (Scanned from the applicant's abstract) Glucocorticoids are assumed to act at the brain to exert their feedback effects. However, there is little, if any evidence that glucocorticoid feedback acts at specific brain sites to maintain basal CRF and ACTH secretion. There is a major effect of glucocorticoids on energy balance exerted in the periphery (on liver, fat, muscle). We hypthesize that glucocorticoid feedback on basal CRF and ACTH secretion is not on brain, but is indirect and consequence of systemic actions of glucocorticoids on metabolism, stimulating metabolic signals that in turn act on brain to normalize activity in the HPA axis (i.e., a brain- glucocorticoid-metabolic-brain axis). We have a powerful tool ( the use of sucrose) with which to test this hypothesis. Adrenalectomized rats drinking sucrose normalize both their behaviors and energy balance compared to Sham. Sucrose also normalizes CRF mRNA in the paraventricular nuclei and amygdala and dopamine-beta-Hydroxylase (DBH) mRNA in catecholaminergic cell groups (nucleus tractus solitarius and locus coeruleus) in ADX rats. We propose to test our hypothesis by determining whether 1. sucrose-induced changes in DBH and CRF are mediated from brainstem to hypothalamus, vice-versa or independently, 2. sucrose-induced changes in paraventricular nuclei (PVN) CRF are dependent on the bed mucleus of the stria terminalis (BNST) or amygdala, and 3. the metabolic signals of sucrose drinking affect the brain via: (a) neural afferents from hepathic vagus, (b) leptin, and (c) brain malony-CoA system. Indiviuals suffering from depression, anorexia, type II diabetes, or Abdominal obesity usually present with altered activity in the HPA axis. These studies will be important for developing a new framework with which to understand the etiologies of such health problems.
|Effective start/end date||5/1/01 → 8/31/02|
- National Institutes of Health: $16,314.00
- National Institutes of Health: $40,196.00
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