Projektbeschreibung
Die Auswirkungen von nächtlichem Licht auf die zirkadiane Uhr
Zirkadiane Rhythmen bestimmen das Muster unserer Tage und Nächte. Es handelt sich um die innere Uhr des Körpers, die unseren Schlaf-Wach-Rhythmus über einen Zeitraum von 24 Stunden reguliert. Die Erfindung der elektrischen Glühbirne und die Lichtexposition bei Nacht hat eine Schattenseite. Sie kann unsere biologische Uhr durcheinanderbringen. Das EU-finanzierte Projekt DiurnalHealth untersucht die Mechanismen, welche den suprachiasmatischen Nukleus – den zentralen Zeitgeber der Säugetiere – beim Menschen und anderen tagaktiven Arten bestimmen. Das Projekt prüft die Hypothese, dass sich die Mechanismen zwischen tag- und nachtaktiven Arten unterscheiden. Es werden die Ähnlichkeiten und Unterschiede im Hinblick auf die Reaktion auf Licht, neuronale Synchronisierung, Ausgangsleistung und Reaktionen auf physische Aktivitäten ermittelt.
Ziel
Due to a significant increase in the use of artificial light in our 24h economy, the biological clocks of all living organisms, including humans, are severely disrupted. Many severe health disorders are consequences of clock disruption such as diabetes, sleep/mood disorders, cardiovascular disease, and immune dysfunction. The central timekeeper in mammals is the suprachiasmatic nucleus (SCN), and the mechanisms by which light disrupts integrity of the SCN has been well investigated in nocturnal species. In contrast, mechanisms of clock disruption in humans and other diurnal (day-active) species remain poorly defined. I have evidence that the mechanisms that drive SCN function are fundamentally different between nocturnal species and diurnal species. This defines my aim to restore proper clock function in diurnal species, including humans. To test this, in Objective 1 we will identify similarities and differences between nocturnal and diurnal clocks with respect to their i) response to light, ii) neuronal synchronization, iii) output, and iv) response to physical activity. Based on these findings, in Objective 2 we will develop novel strategies to manipulate and restore clock function in diurnal species. These objectives will be achieved using novel, state-of-the-art chronobiology methods including in vivo electrophysiology and Ca2+ and bioluminescence reporters—all in freely behaving day-active animals, as well as in slice preparations containing the SCN. For studies on the human SCN we record with 7-Tesla fMRI. This proposal will help establish a new basis for chronobiology with respect to the most suitable models for studying translational applications. The results will yield immediate benefits in terms of manipulating biological clock function among vulnerable populations in modern society, particularly the elderly, patients in intensive care, and shift workers.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-ADG - Advanced GrantGastgebende Einrichtung
2333 ZA Leiden
Niederlande