Zirkadiane Uhren in Gehirn und Peripherie: biologische Funktion und Relevanz für die Klinik

Zusammenfassung

In den meisten Organismen – von Cyanobakterien bis zum Menschen – haben sich genetisch kodierte zirkadiane Uhren entwickelt, die Verhalten und Physiologie an im Tagesverlauf veränderliche Umweltbedingungen adaptieren. Störungen der Uhr, zum Beispiel durch Schichtarbeit, beeinträchtigen diese Anpassung und fördern so die Entwicklung von metabolischen, immunologischen und neuropsychiatrischen Erkrankungen. Das zirkadiane System der Säugetiere besteht aus einem zentralen Schrittmacher im Nucleus suprachiasmaticus des Hypothalamus und untergeordneten, semi-autonomen Uhren in, unter anderem, der Leber, der Niere, der Nebenniere, aber auch in vielen weiteren Hirnregionen. Während periphere Oszillatoren endokrine, metabolische und immunologische Prozesse regulieren, modulieren zentrale Uhren grundlegende wie höhere Hirnfunktionen. In Klinik und Praxis hilft die Kenntnis dieser physiologischen Rhythmen bei der Interpretation von Labordaten und anderen Krankheitssymptomen. Die Chronomedizin kann durch Anpassung der Behandlungszeiten die Wirksamkeit und Nebenwirkungen von Therapien optimieren oder über eine Stabilisierung des internen zirkadianen Rhythmus den Krankheitsstatus direkt beeinflussen.

Abstract

In most species – from cyanobacteria to humans – genetically encoded circadian clocks have evolved to adapt behavioral and physiological processes to environmental changes brought about by the Earth's rotation. Clock disruption, e. g. by shift work, can lead to circadian misalignment, promoting the development of metabolic, immune and cognitive dysfunction. In mammals, a central circadian pacemaker residing in the suprachiasmatic nuclei of the hypothalamus resets subordinate, but semi-independent cellular clocks in tissues such as liver, kidney, adrenal, and many brain areas. Peripheral clocks regulate various endocrine, metabolic and immune processes, whereas central oscillators modulate basic as well as higher brain functions. For the clinical practice it is of major importance to be aware of these physiological rhythms in order to correctly interpret laboratory data and other disease symptoms. Chronomedical therapies can reduce side effects and increase efficacy by optimizing the timing of treatment or directly affect disease state by restoring internal circadian synchrony.

Schlüsselwörter

zirkadiane Rhythmen - periphere Uhren - Chronophysiologie - Chronomedizin

Keywords

circadian rhythms - peripheral clocks - chronophysiology - chronomedicine

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