Ziel
Population statistics demonstrate drastically increased risk of cardiovascular death with increasing body mass index. Given the current obesity epidemic our need to understand the central neuronal pathways regulating energy homeostasis and cardiovascular function could not be greater.
This proposal aims to determine key neuronal pathways mediating melanocortin's autonomic effects on cardiovascular function. It combines molecular genetics and whole animal physiology to advance translational research in the development of effective therapies against obesity-induced hypertension. Recent evidence suggests that both obesity and essential hypertension are associated with increased sympathetic nerve activity. Increased sympatho-activation in obesity-associated hypertension has been linked to increases in central signalling via the melanocortin-4-receptor (MC4R).
We hypothesize that the pressor actions of obesity are mediated via specific MC4Rs on central neurons regulating arterial blood pressure. We will investigate which subpopulation of MC4Rs mediates melanocortin's effects on cardiovascular function using functional genomics approaches, including an MC4R deficient mouse, in which a disrupted MC4R can be reactivated in specific CNS areas by the actions of Cre-recombinase. Using in vivo mouse telemetry we will thus determine the neuronal pathways involved in melanocortin-mediated regulation of cardiovascular function and define the MC4R¿s role in obesity-induced activation of the sympathetic nervous system.
This proposal is absolutely consistent with the Sixth (and future 7th) Framework Programme, placing particular emphasis on functional genomics and the combat against major diseases such as hypertension. Furthermore, it brings significant skills in state-of-the-art generation of mouse models relevant to human disease, in combination with sophisticated physiological techniques to the European Research Area, thereby increasing its attractiveness to young researchers.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesgenetics
- natural sciencesbiological sciencesmolecular biologymolecular genetics
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- medical and health sciencesbasic medicinephysiologyhomeostasis
- medical and health scienceshealth sciencesnutritionobesity
Schlüsselbegriffe
Aufforderung zur Vorschlagseinreichung
FP6-2004-MOBILITY-12
Andere Projekte für diesen Aufruf anzeigen
Finanzierungsplan
IRG - Marie Curie actions-International re-integration grantsKoordinator
BRISTOL
Vereinigtes Königreich