Project description
Dopamine signalling in the central brain clock and a potential role in metabolic syndrome
The circadian system regulates daily rhythms of bodily functions, including sleep, appetite, and hormone release. Circadian rhythms are produced by the central brain clock in the hypothalamic suprachiasmatic nuclei (SCN) and are primarily entrained by retinal light input; they are also modulated by other cues including exercise and food intake. Circadian rhythm disruption can lead to cardiometabolic diseases, but the underlying mechanisms are unclear. Dopamine might play a role as a non-photic cue, providing feedback to the SCN about the body’s metabolic state. With the support of the Marie Skłodowska-Curie Actions programme, the DopaClock project aims to investigate the link between dopamine, the SCN, diet-induced obesity, and cardiometabolic diseases.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicinephysiologyhomeostasis
- medical and health scienceshealth sciencesnutritionobesity
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
1081 HV Amsterdam
Netherlands