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Circadian oscillations of neuropeptide expression in the human biological clock

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Abstract

The mammalian suprachiasmatic nucleus is the principal component of a neural timing system implicated in the temporal organization of circadian and seasonal processes. The present study was performed to analyze the circadian profiles of two major neuropeptidergic cell groups in the human suprachiasmatic nucleus. To that end the brains of 40 human subjects collected at autopsy were investigated. The populations of arginine vasopressin- and vasoactive intestinal polypeptide-expressing neurons, located in the shell and core of the suprachiasmatic nucleus, respectively, showed marked circadian rhythms with an asymmetrical, bimodal waveform. Time series analysis revealed that these circadian cycles in neuronal activity could be described by a composite model consisting of a nonlinear periodic function, with mono- and diphasic cycles. The findings suggest that the 24-h biosynthesis of neuropeptides in the human suprachiasmatic nucleus, being part of the neural output pathway of the clock, is driven by a complex pacemaker system consisting of coupled nonlinear oscillators, in accordance with a multioscillator model of circadian timekeeping.

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Abbreviations

AIC:

Akaikie's information criterion

ARMA:

autoregressive moving average

AVP:

arginine vasopressin

c-fos :

immediate early gene

Per :

period gene

SCN:

suprachiasmatic nucleus

VIP:

vasoactive intestinal polypeptide

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Acknowledgements

The author wishes to thank Prof. D.F. Swaab and Dr. J.N. Zhou for providing the morphometric data and Mr. H. Stoffels for preparing the figures. Brain material was obtained from the Netherlands Brain Bank, Amsterdam (coordinator Dr. R. Ravid).

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Correspondence to M. A. Hofman.

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Hofman, M.A. Circadian oscillations of neuropeptide expression in the human biological clock. J Comp Physiol A 189, 823–831 (2003). https://doi.org/10.1007/s00359-003-0458-3

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  • DOI: https://doi.org/10.1007/s00359-003-0458-3

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