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The manipulation of circadian rhythms

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Abstract

In a study on male Wistar (TNO) rats kept under phase-shifted light-dark (12∶12) conditions, it was demonstrated that the circadian rhythms of the following functions were effectively synchronized to the new lighting regimen: (a) body temperature, gross motor activity (after 1 week of acclimatization); (b) stomach weight, liver weight, liver glycogen, liver protein and acid phosphatase activity; serum corticosterone, glucose, total protein and inorganic phosphate (after 4–6 weeks; as concluded from the data pooled of a set of identical experiments); (c) the in vivo toxicity of ∼ LD50 amounts (i.p.) for antimycin A and of E 600. In the individual experiments the various normal functions appeared to be different with respect to sensitivity to light. The overall pooled results indicated that, except for glycogen, the 24-h means of the normal values in the stomach, liver and serum were slightly decreased when compared to the respective means obtained from standard LD (= light: 6:00–18:00) -conditioned control groups (P < 0.001 for liver weight, liver protein, serum protein and inorganic phosphate). The experimental animals revealed an intermediate or persisting decrease of the growth rate. From the serial biological and toxicological studies performed in the course of 1 year, it is concluded that the synchronizing effect of an altered lighting regimen may be influenced by seasonal factors.

Under certain conditions the use of light-manipulated animals will prove to be a useful tool in chronobiology and chronotoxicology.

Zusammenfassung

An ad lib. gefütterten männlichen Wistar (TNO) Ratten wurde nachgewiesen, daß die Tagesrhythmik folgender Funktionsgrößen durch die Wirkung von phasen-verschobenen Licht-Dunkel (12∶12)-Verhältnissen synchronisiert wird: (a) nach 1 Woche Akklimatisierung, Körpertemperatur und Bewegungsaktivität; (b) nach 4–6 Wochen, Magen- und Lebergewicht, Leberglykogen,-protein und saure Phosphatase, Serumcorticosteron, -gesamtprotein,-glukose und anorganisches Phosphat (gemittelte Meßergebnisse über mehrere Experimente); (c) nach 4–6 Wochen, die Sterblichkeitsrate nach i.p.-Injektion von ∼ LD50-Mengen von Antimycin A oder E 600. Hinsichtlich der Lichtempfindlichkeit kamen in den Einzelversuchen deutliche Unterschiede zwischen den verschiedenen Normalfunktionen zum Ausdruck. In den gemittelten Meßergebnissen waren die 24-Stundenmittel der Organ- und Serumwerte gegenüber den parallel untersuchten, LD (= Licht: 06.00–18.00) -standardisierten Kontrollen geringfügig erniedrigt (P < 0,001 für Lebergewicht, Leberprotein, Serumprotein und anorg. Phosphat). Die Wachstumsrate der Versuchstiere zeigte eine vorübergehende oder bleibende Verlangsamung. Die während einem Jahr mehrfach durchgeführten biologischen und toxicologischen Untersuchungen zeigten, daß die Anpassungsfähigkeit des Organismus an neue Licht-Dunkelverhältnisse möglicherweise auch jahreszeitlichen Einflüssen unterliegt.

Unter geeigneten Bedingungen erweist sich die Untersuchung der Circadianrhythmik im Licht-manipulierten Organismus der Ratte als brauchbare Methode für Chronobiologie und Chronotoxicologie.

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Authors and Affiliations

  1. Institut für Anatomie, Abt. I Medizinische Hochschule, Karl-Wiechert-Allee 9, D-3000, Hannover, Federal Republic of Germany

    Karel M. H. Philippens

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  1. Karel M. H. Philippens
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Read at the Symposium “Relevance of Chronobiology for Toxicology and Pharmacology” held at the 16th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Section: Toxicology, March 6, 1975, Mainz

Supported by grants from Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 146 (Versuchstierkunde) and VW-Stiftung, Hannover AZ 11.2000

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Philippens, K.M.H. The manipulation of circadian rhythms. Arch. Toxicol. 36, 277–303 (1976). https://doi.org/10.1007/BF00340535

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