The SCN Metabolome

Stephan Michel (LUMC)

A dysfunctional circadian clock is associated with diseases like metabolic syndrome, cardiovascular diseases, but also neurological disorders, like Huntington, Alzheimer and certain forms of depression. The dysfunctions of the clock, like a lower amplitude signal generated in the master mammalian pacemaker residing in the suprachiasmatic nucleus (SCN), can result from a lack of synchrony among the neuronal network of the SCN. It has been documented that aging affects the amplitude of SCN rhythm, which may contribute to sleep-wake rhythm deterioration, but also circadian dysfunction in neurodegenerative diseases.

We will use experimental protocols and different animal models to study dysfunctional circadian clocks. We will identify markers for neuronal pacemaker functions, intercellular communication and homeostasis in SCN slices. Our approach will furthermore employ metabolomic profiling, a technique previously used for studying the biochemical milieu of neurodegenerative diseases in animal models and as a diagnostic tool for brain damage. This method was recently applied to detection of circadian disturbances. We will correlate these data with measurement of intracellular calcium, an important intracellular messenger for the clock function, and electrophysiological techniques.