Die Uhr im Hypothalamus

Zusammenfassung

Der vorliegende Beitrag befasst sich auf der Grundlage tierexperimenteller Daten mit neurobiologischen Grundlagen des zirkadianen Systems und gibt einen kurzen Ausblick auf pathophysiologische Aspekte. Das zirkadiane System steuert zahlreiche rhythmische Körperfunktionen. Der Schrittmacher des zirkadianen Systems der Säugetiere und des Menschen ist der Nucleus suprachiasmaticus (SCN) des Hypothalamus, der durch transkriptional/translationale Rückkopplungsschleifen zwischen Uhrengenen und ihren Proteinprodukten einen endogenen Rhythmus mit einer Periodenlänge von ca. 24 Stunden generiert. Dieser endogene, zirkadiane Rhythmus wird durch Umweltreize, als Zeitgeber bezeichnet, mit dem Tag-Nacht-Rhythmus synchronisiert. Der wichtigste Zeitgeber ist der Hell-Dunkelwechsel, der von verschiedenen Photorezeptortypen in der Netzhaut wahrgenommen und über den retinohypothalamischen Trakt an den SCN übertragen wird. Die “zentrale” Uhr im SCN vermittelt ihre Signale über neuroendokrine und neuronale Mechanismen an “periphere” Oszillatoren, die sowohl im Zentralnervensystem als auch in der Körperperipherie lokalisiert sind. Mäuse mit molekulargenetischen Veränderungen des zirkadianen Systems zeigen Schlafstörungen, Veränderungen im Gehalt von Neurotransmittern und scheinen suchtanfällig zu sein. In Zukunft wird zu untersuchen sein, ob Polymorphismen der Uhrengene auch mit neuropsychiatrischen Veränderungen beim Menschen einhergehen.

Summary

This contribution reviews data from experimental animals on neurobiological aspects of the circadian system and provides a short outlook on pathophysiological consequences of molecular genetic alterations in the circadian system. In the center of the mammalian circadian system that controls a variety of rhythmic functions is the suprachiasmatic nucleus (SCN) of the hypothalamus. By transcriptional/translational feedback loops between clock genes and their protein products the SCN generates an endogenous rhythm with a period of approximately 24 hours. This circadian rhythm is entrained to the environment by external stimuli called zeitgebers. The most important zeitgeber is the photoperiod. In mammals photoperiodic stimuli are percveived in the retina by different types of photoreceptors and are transmitted to the SCN via the retino hypothalamic tract.The “central” circadian clock in the SCN conveys its signals via neuroendocrine and neuronal mechanisms to “peripheral” oscillators located either in the central nervous system or in other organs. Mice with mutations in clock genes display abnormalities in behavior and alterations in several neurotransmitter systems. These experimental data suggest that central nervous system diseases in man may be accompanied by clock gene polymorphisms.

Schlüsselwörter

Zirkadiane Rhythmen - Nucleus suprachiasmaticus - Uhrengene

Keywords

Circadian rhythms - clock genes - suprachiasmatic nucleus

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