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Novel energy-sensing pathways in the brain

Reference	BB/F00172X/1
Principal Investigator / Supervisor	Professor Denis Burdakov
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Pharmacology
Funding type	Research
Value (£)	283,961
Status	Completed
Type	Research Grant
Start date	01/10/2007
End date	30/09/2010
Duration	36 months

Abstract

How body energy levels are translated into appropriate feeding behaviours is a fundamental unsolved question in mammalian biology. We know: 1) that hypothalamic orexin neurons are essential for translating falling energy levels into food-seeking, 2) that glucose is the key signal informing the brain of energy levels, and 3) that glucose blocks the electrical activity of orexin neurons by stimulating K+ channels. However, nothing is known about a) how glucose turns on these inhibitory K+ channels, and b) whether glucose-induced inhibition via K+ channels is important in controlling other neurons that regulate feeding. In this research programme we will use techniques and animal models that have been very successful in the study of orexin neurons and cellular mechanisms of glucose-sensing, and combine them to identify cellular signalling pathways by which glucose blocks the electrical activity of orexin neurons and other feeding-regulating hypothalamic cells. These investigations will provide fundamental new insights into energy-sensing by eukaryotic cells, with important implications for physiology and pathophysiology of body weight regulation.

Summary

Blood sugar goes up and down between meals, telling the brain when it is time to start and stop eating. If this natural communication between energy levels and behaviour goes wrong, sleep and body weight go awry, leading to insomnia, obesity, anorexia, or excessive sleepiness. For a long time it remained a mystery how eating controls the brain, but scientists recently found that glucose, the sugar in the blood which goes up after meals, turns off brain cells that make us awake and hungry. This is exciting because it can explain common experiences such as feeling sleepy after a meal, but at the same time it is mysterious because sugar is an energy fuel, and usually it turns cells on not off. In our research, we are seeking to understand exactly how sugar turns off the special type of brain cell that makes us awake and hungry.

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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