(Year 2 of this project)
In patients suffering from Prader-Willi syndrome, it has been shown that there is a greatly elevated level of a hormone known as ghrelin. This hormone is known to normally stimulate hunger and food intake. However, the levels of the circulating hormone leptin that signals the need to reduce food intake and increase energy expenditure is not similarly upregulated. Consequently, it is possible that the imbalance between these hormones is responsible for the insatiable appetite of Prader-Willi syndrome. It is feasible that if the effects of ghrelin could be blocked, these symptoms could be relieved.
Before this can become a reality, it is first necessary to fully appreciate how this hormone works to stimulate hunger. We believe it does so by acting upon a specific group of neurons in the brain. So far the actions of ghrelin on these neurons has not been studied because up to now they have been difficult to identify. However, the investigators have now resolved this problem and are in a position where they can explore how ghrelin works in these neurons to stimulate appetite. The long-term aim of these studies is to identify drugs which will regulate the action of this hormone and are therefore able to regulate the appetite in those individuals where it is over produced such as in the case of Prader-Willi syndrome.
Research Outcomes:
Pharmacological and molecular characterization of ATP-sensitive K+ conductances in CART and NPY/AgRP expressing neurons of the hypothalamic arcuate nucleus. van den Top M, Lyons DJ, Lee K, Coderre E, Renaud LP, Spanswick D. Neuroscience. 144:815-824, 2007.
Integration of metabolic stimuli in the hypothalamic arcuate nucleus. van den Top M, Spanswick D. Progress Brain Research. 153:141-154, 2006.
Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus. van den Top M, Lee K, Whyment AD, Blanks AM, Spanswick D. Nature Neuroscience. 7:493, 2004.
Funded Year:
2005
Awarded to:
David Spanswick, Ph.D
Amount:
$20,000
Institution:
Department of Neuroscience, University of Warwick, UK
