Int. J. Mol. Sci. 2013, 14(3), 5817-5841; doi:10.3390/ijms14035817
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Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction

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Received: 17 February 2013; in revised form: 1 March 2013 / Accepted: 4 March 2013 / Published: 12 March 2013
(This article belongs to the Special Issue Advances in the Research of Melatonin)
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Abstract: The mammalian circadian system is composed of numerous oscillators, which gradually differ with regard to their dependence on the pacemaker, the suprachiasmatic nucleus (SCN). Actions of melatonin on extra-SCN oscillators represent an emerging field. Melatonin receptors are widely expressed in numerous peripheral and central nervous tissues. Therefore, the circadian rhythm of circulating, pineal-derived melatonin can have profound consequences for the temporal organization of almost all organs, without necessarily involving the melatonin feedback to the suprachiasmatic nucleus. Experiments with melatonin-deficient mouse strains, pinealectomized animals and melatonin receptor knockouts, as well as phase-shifting experiments with explants, reveal a chronobiological role of melatonin in various tissues. In addition to directly steering melatonin-regulated gene expression, the pineal hormone is required for the rhythmic expression of circadian oscillator genes in peripheral organs and to enhance the coupling of parallel oscillators within the same tissue. It exerts additional effects by modulating the secretion of other hormones. The importance of melatonin for numerous organs is underlined by the association of various diseases with gene polymorphisms concerning melatonin receptors and the melatonin biosynthetic pathway. The possibilities and limits of melatonergic treatment are discussed with regard to reductions of melatonin during aging and in various diseases.
Keywords: age-related diseases; aging; circadian; melatonergic agonists; melatonin; MT1; MT2; peripheral oscillators; polymorphisms
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Hardeland, R. Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction. Int. J. Mol. Sci. 2013, 14, 5817-5841.

AMA Style

Hardeland R. Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction. International Journal of Molecular Sciences. 2013; 14(3):5817-5841.

Chicago/Turabian Style

Hardeland, Rüdiger. 2013. "Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus—Consequences to Melatonin Dysfunction." Int. J. Mol. Sci. 14, no. 3: 5817-5841.


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