The role of dopamine signalling in the central clock in the model of metabolic s...
The role of dopamine signalling in the central clock in the model of metabolic syndrome
The internal daily rhythms of an organism are driven by the circadian timing system. The master clock is in the brain hypothalamic suprachiasmatic nuclei (SCN). SCN rhythms are entrained to the 24h environmental light/dark cycle b...
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Información proyecto DopaClock
Duración del proyecto: 29 meses
Fecha Inicio: 2024-04-19
Fecha Fin: 2026-09-30
Líder del proyecto
STICHTING AMSTERDAM UMC
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
203K€
Descripción del proyecto
The internal daily rhythms of an organism are driven by the circadian timing system. The master clock is in the brain hypothalamic suprachiasmatic nuclei (SCN). SCN rhythms are entrained to the 24h environmental light/dark cycle by retinal light input, but also respond to non-photic cues (e.g., food intake) transmitted via neuronal projections from other brain areas. Disruption of daily rhythms can lead to cardiometabolic diseases, but the underlying mechanisms are unclear. Recent evidence challenges the belief that the SCN is only sensitive to dopamine (DA) in early development; it appears that DA affects SCN function also in adults. In the brain reward system, DA is linked to binge-eating in animals on a high-fat diet. We hypothesise that DA acts as a non-photic cue in the SCN, providing feedback information on metabolic status which can be disturbed by diet-induced obesity. This project’s main aim is to delineate the cardiometabolic effects of DA in the central SCN clock. My objectives are to define the effects of DA signalling in the SCN on 1) energy metabolism, 2) glucose homeostasis and the cardiovascular system and 3) these cardiometabolic parameters under obese conditions. To achieve my goals, I will combine supervisor’s expertise in the central circadian control of energy metabolism, along with specialized techniques and equipment, with my knowledge in cardiovascular measurements using radiotelemetry. I will use rats expressing Cre recombinase in dopamine D1 receptor-neurons and targeted viral injections, an innovative technique to mimic DA signalling in the SCN (the secondment). Project findings will fill the knowledge gap in neural mechanisms behind the adverse effects of circadian disturbance on energy homeostasis and could help to improve lifestyles of patients with cardiometabolic diseases. This MSCA-PF-supported project will enhance my technical and transferable skills, facilitating my path to becoming an independent researcher in chronobiology.