Exeter Postdoc Appreciation Week - Thu Seminar

The day-night cycle governs our physiology, within the brain lies the control centre, the suprachiasmatic nucleus (SCN). The SCN is thought to communication with peripheral clocks throughout the body to regulate diurnal rhythmicity. One such peripheral clock could exist within sympathetic preganglionic neurons (SPNs) which are the final point of influence the central nervous system has on sympathetic nerve activity. Our findings suggest that SPNs contain circadian clock machinery which may control expression of genes/proteins that influence SPN and sympathetic nerve activity.

Type 2 diabetes mellitus (T2DM) and neurodegenerative disease such as Alzheimer’s disease share common pathophysiological characteristics such as insulin resistance and decreased glucose metabolism. GLP-1 receptor agonists are used as treatments for patients with T2DM, however some of these drugs also have beneficial effects in the brain. Here, we use GLP-1 receptor activation to study the effects of such drugs on neuronal activity. Our works will provide a basis for future works to study whether the effects of GLP-1R activation on neuronal activity is a result of direct or modulatory mechanism, and also how the regulation of neural circuits by this receptor system guides behaviour.

Historically, it was believed that the master clock in the suprachiasmatic nucleus of the hypothalamus controls all daily rhythms in physiology and behaviour. Here, we present novel findings on the existence of the autonomous circadian timekeeping centre in the brainstem dorsal vagal complex (DVC) of mice and rats. We further characterise its physiological relevance and disturbance under high-fat diet, what is reflected in blunted daily rhythms of food intake. Our findings have clear implications for future chronotherapy of obesity.