Behavioural and neuroendocrine mechanisms regulating hydromineral metabolism: a lifelong perpective

Resumo

The bodily fluids of the mammalian organism are in a perpetual state of flux. Integrated neuroendocrine and behavioral mechanisms function to control the execration and consumption of water and salt in order to maintain the optimal bodily content required for good health. These systems deteriorate with old age, and are perturbed by exposure to high salt in utero. The paraventricular nucleus (PVN) of the endocrine hypothalamus is well known for its role in the elaboration of a hormone, arginine vasopressin (AVP), that promotes water conservation at the level of the kidney. We have catalogued the transcriptome of the PVN, and described how it changes as a consequence of fluid deprivation. For example, dehydration results in the dramatic up-regulation of transcription factor gonadotrophin inducible transcription factor 1 (Giot1). Viral vector mediated inhibition of Giot1 has provided exciting new evidence that suggest that the PVN is involved in generating the instincts that control the consumption of salt; shRNA-mediated suppression of expression of Giot1 in the PVN results in a rat devoid of salt appetite. We thus hypothesize: i) that the PVN has an integrative role, coordinating the neuroendocrine and behavioral responses to hydromineral imbalance; ii) that these integrative functions are perturbed in old age, resulting in decreased thirst perception, reduced sodium appetite, and altered activity of AVP neurons; iii) that these integrative functions are perturbed by foetal exposure to high salt, resulting in a reprogramming of the set point for adult salt consumption. (AU)