The hypothalamus is essential for the maintainance of extracellular volume and tonicity, as well as energy homeostasis. In this study we aim to clarify the involvement of neuronal and glial components in the integrative responses, as well as the participation of key neurotransmitters, neuromodulators, hormones and neuropeptides in the neuroendocrine control of both water and sodium intake and excretion and food intake. Considering that maternal nutritional and hormonal factors strongly affect fetal/neonatal programming, which affects metabolic function in adult life, this study also aims to evaluate the effects of saline overload during pregnancy and lactation and its repercussions to the integrity of neuroendocrine responses in adulthood. We will also investigate the participation of central mediators of appetite and peripheral factors such as insulin, leptin, ghrelin, adiponectin, glucocorticoids and estrogen in energy homeostasis using experimental models of bilateral adrenalectomy, ovariectomy and endotoxin tolerance. The peak of glucocorticoid secretion occurs in accordance with feedind pattern, with interplay between hypothalamic-pituitary-adrenal axis activity, central nervous system and nutritional status. The hypothalamus acts as a integrative center of circadian rhythm and also of glucocorticoid secretion and energy homeostasis, integrating neuroendocrine and behavioral responses. Thus, in the present study, we will evaluate the expression of genes related with circadian rhythm and its correlation with orexigenic and anorexigenic neuropeptides. We will also evaluate the ontogeny of clock genes and diurnal secretion of corticosterone in rats. Therefore, this proposal, using in vivo and in vitro experimental models, aims to assess in an integrative view, from molecules to systems, the physiological and pathophysiological control of energy homeostasis and fluid balance.
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