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Behavioural and neuroendocrine mechanisms regulating hydromineral metabolism: a lifelong perpective


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)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Cientistas tentam identificar genes-chave para o controle de funções vitais 

Publicações científicas
(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)
GREENWOOD, MICHAEL P.; GREENWOOD, MINGKWAN; MECAWI, ANDRE S.; ANTUNES-RODRIGUES, JOSE; PATON, JULIAN F. R.; MURPHY, DAVID. Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation. MOLECULAR BRAIN, v. 9, JAN 7 2016. Citações Web of Science: 6.
GREENWOOD, MINGKWAN; GREENWOOD, MICHAEL P.; MECAWI, ANDRE S.; LOH, SU YI; RODRIGUES, JOSE ANTUNES; PATON, JULIAN F. R.; MURPHY, DAVID. Transcription factor CREB3L1 mediates cAMP and glucocorticoid regulation of arginine vasopressin gene transcription in the rat hypothalamus. MOLECULAR BRAIN, v. 8, OCT 26 2015. Citações Web of Science: 6.

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