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Behavioural and neuroendocrine mechanisms regulating hydromineral metabolism: a lifelong perpective

Grant number: 11/52108-4
Support type:Research Projects - Thematic Grants
Duration: November 01, 2012 - October 31, 2015
Field of knowledge:Biological Sciences - Physiology
Cooperation agreement: BBSRC, UKRI
Principal Investigator:José Antunes Rodrigues
Grantee:José Antunes Rodrigues
Principal investigator abroad: David Murphy
Institution abroad: University of Bristol, England
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):13/26072-8 - PARTICIPATION OF NITRERGIC SYSTEM IN THE NEUROENDOCRINE AND BEHAVIORAL RESPONSES INDUCED BY OSMOTIC STIMULI, BP.PD

Abstract

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)

Articles published in Agência FAPESP Newsletter about the research grant:
Scientists attempt to identify key genes to control vital functions 

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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. Web of Science Citations: 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. Web of Science Citations: 6.

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