Periodic Reporting for period 3 - DiurnalHealth (The circadian clock in day-active species: preserving our health in modern society)
Periodo di rendicontazione: 2022-09-01 al 2024-02-29
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 tentative 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.
Equipment, such as fMRI-usable LED stimulus glasses and diurnal species facilities (cages, and more), has been developed and fMRI studies have been performed.
In vivo and in vitro imaging techniques for diurnal species are on schedule. We have successfully obtained expression of the calcium reporter GCaMP in the brain using viral vectors, and we are in the process of collecting imaging data.
One human study has been finished in which we investigated the association between continuous ambulatory heart rate, heart rate variability, and 24-h rhythms of heart rate with familial longevity and aging.
In vivo and in vitro imaging techniques for diurnal species are on schedule. We have successfully obtained expression of the calcium reporter GCaMP in the brain using viral vectors, and we are in the process of collecting imaging data.
One human study has been finished in which we investigated the association between continuous ambulatory heart rate, heart rate variability, and 24-h rhythms of heart rate with familial longevity and aging.
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.