[Circadian rhythm study from anticipatory behavior to drug treatment].

Nov 30, 2005Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology

How Daily Body Clocks Affect Anticipatory Behavior and Response to Drug Treatment

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Abstract

Mice experienced a 6-12 hour advance in the peaks of mPer1 and mPer2 mRNA in the cerebral cortex and liver after 6 days of restricted feeding.

Circadian rhythms are influenced by both the light-dark cycle and feeding schedules.
Light induces the expression of clock genes Per1 and Per2 in the suprachiasmatic nucleus (SCN), which regulates the internal clock.
Restricted feeding can advance the expression of clock genes in tissues such as the cerebral cortex and liver.
The effects of restricted feeding on mPer expression occur independently of the SCN's light-dependent clock functions.
Increased mPer expression was observed even in mice with lesions in the SCN, indicating alternative pathways for circadian modulation.

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Precise, rhythmic, daily change of the internal milieu is a conspicuous feature of all living organisms. It affects temporal patterns of all kinds of behaviors during a day and deeply influences both the social structure and daily life of individual human beings. These daily variations arise from the internal circadian mechanisms. Three functions of the endogenous clock are discriminated as rhythm generation, entrainment to light-dark cycle and output from the clock. The endogenous clock is localized in the suprachiasmatic nucleus (SCN) in mammals. Recent papers demonstrated strong expression of clock genes such as Per1, Per2 and Per3 in the SCN. Circadian oscillation is basically regulated by the transcription/translation feedback system of the Per gene in mammals. As serotonin/antidepressant and GABA/benzodiazepine drugs affect the light and non-light-induced entrainment, these drugs can regulate the circadian oscillation of clock genes and environmental stimuli-induced change of Per gene expression in the SCN. There are two main stimuli that entrain circadian rhythm, the light-dark cycle (LD) and restricted feeding. Light resets the circadian clock with induction of Per1 and Per2 gene in the SCN, the locus of a main oscillator. Mice were allowed access to food for 4 h during daytime (7 h in advance of feeding time) under LD or constant darkness. The peaks of mPer1 and mPer2 mRNA in the cerebral cortex and liver were advanced 6-12 h after 6 days of RF, whereas those in SCN were unaffected. The increase of mPer expression by RF treatment was observed in SCN-lesioned mice. The present results suggest that RF strongly entrained the expression of mPer and clock-controlled genes in the cerebral cortex and liver without affecting light-dependent SCN clock function.

[Circadian rhythm study from anticipatory behavior to drug treatment].

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