USA - Novel insights into the mechanisms of salt appetite

Lead Research Organisation: University of Bristol
Department Name: Clinical Science at South Bristol

Abstract

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Description Working with our collaborators in Illinois, we have combined transcriptome analysis with proteomics to better understand how the hypothalamus responds to the stress of dehydration, and how this changes with ageing. Dehydration is normally associated with an increase in the secretion of the antidiuretic hormone vasopressin (AVP) from the posterior pituitary, and a concomitant increase in its biosynthesis in the hypothalamus. Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states. In the SON, increased AVPO gene transcription, coincided with reduced AVP gene promoter methylation in aged rats. Based on transcriptome data, we have previously characterized a number of novel dehydration-induced regulatory factors involved in the response of the SON to osmotic cues. We found that some of these increase in expression with age, while dehydration-induced expression of these genes in the SON was attenuated in aged rats. In summary, we show that aging alters the rat AVP system at the genome, transcriptome, and peptidome levels.
Exploitation Route We are continuing to work with our Illinois collaborators on a number of projects related to the hypothalamic control of homeostasis, and the effects of ageing.
Sectors Healthcare

Pharmaceuticals and Medical Biotechnology
 
Description Hydromineral homeostasis collaboration (Brazil) 
Organisation Universidade de São Paulo
Department Department of Physiology and Biophysics
Country Brazil 
Sector Academic/University 
PI Contribution Project jointly funded by FAFESP and BBSRC
Collaborator Contribution Project jointly funded by FAFESP and BBSRC
Impact None as yet
Start Year 2012
 
Description Illinois collaboration 
Organisation University of Illinois at Urbana-Champaign
Department The Department of Chemistry
Country United States 
Sector Academic/University 
PI Contribution Expertise is transcriptomics and the physiology and behaviour of hydromineral homeostasis, salt appetite and thirst.
Collaborator Contribution Mas spec neuropeptidomics
Impact None as yet
Start Year 2012
 
Description Saudi Arabia collaboration 
Organisation King Saud University
Department Department of Zoology
Country Saudi Arabia 
Sector Academic/University 
PI Contribution Transcriptomic analysis of Jerboa tissues.
Collaborator Contribution Privision of Jerboa tissues.
Impact Not applicable as yet/
Start Year 2018
 
Description UAE collaboration 
Organisation United Arab Emirates University
Department Department of Pharmacology and Therapeutics
Country United Arab Emirates 
Sector Hospitals 
PI Contribution Transciptomic skills and analysis
Collaborator Contribution Provision og physiological data and samples
Impact No out puts as yet. New collaboration.
Start Year 2015