Circadian rhythm perturbation leads to reorganization of suprachiasmatic nucleus network

Lily Yan, PhD

Assistant Professor
Psychology Department
Michigan State University
East Lansing, Michigan

Biological rhythms are controlled by a master central circadian clock located in a pair of nuclei in the brain called the suprachiasmatic nucleus (SCN).1 Tightly regulated by light and darkness to generate circadian information, the SCN is a master time-keeper, sending signals to other parts of the brain and body, and thereby promoting normal peripheral rhythms and functions in other tissues and organ systems.2-4 The precise timing of these peripheral processes may become altered if the SCN’s circadian rhythmicity is disrupted or misaligned by environmental cues. For example, individuals who frequently travel across different time zones are forced to maintain a sleep/wake schedule inconsistent with their internal biological clocks, which affects SCN timing. As a consequence, these individuals may be exposed to additional pathophysiologic processes, including cancer, gastrointestinal disturbances, cognitive dysfunction, mood disorders, and cardiovascular abnormalities.5-8 How perturbations in circadian rhythms alter brain function and affect normal physiologic processes are not well understood and are the focus of considerable research efforts. One study forced circadian disruptions using a weekly phase-shifting paradigm, in which mice were subjected to a 6-hour light/dark cycle once a week for a month; the intended effect was to advance the phase of the biological clock and mimic a world traveler who experiences jet lag after flying to a new location each week. PRO1, a clock gene expressed with circadian rhythmicity, is robustly upregulated in light and downregulated in darkness. To monitor molecular changes associated with regulation of circadian rhythms, researchers from Michigan State University assessed the expression of PRO1. The results showed similar temporal patterns of PRO1 expression when the mice were left in their normal light/dark cycle or were kept in darkness during the shift to a 6-hour light/dark cycle; however, in the latter condition, the amplitude of PRO1 expression was decreased. Hypothesizing that PRO1 is involved in the pathophysiology of circadian rhythm disruptions, the researchers intend to perform additional experiments to elucidate any potential relationship. A better understanding of how the brain responds to circadian disturbances might help prevent and possibly treat misaligned circadian timing, as is observed in shift workers or individuals experiencing jet lag.

References

Cermakian N, Boivin DB. The regulation of central and peripheral circadian clocks in humans. Obes Rev. 2009;10 (Suppl 2):25-36.
Karatsoreos IN, Silver R. Minireview: The neuroendocrinology of the suprachiasmatic nucleus as a conductor of body time in mammals. Endocrinology. 2007;148:5640-5647.
Krauchi K. The thermophysiological cascade leading to sleep initiation in relation to phase of entrainment. Sleep Med Rev. 2007;11:439-451.
Young ME. Anticipating anticipation: pursuing identification of cardiomyocyte circadian clock function. J Appl Physiol. 2009;107:1339-1347.
Erren TC, Reiter RJ. A generalized theory of carcinogenesis due to chronodisruption. Neuro Endocrinol Lett. 2008;29:815-821.
Hoogerwerf WA. Biologic clocks and the gut. Curr Gastroenterol Rep. 2006;8:353-359.
Lewy, AJ. Circadian misalignment in mood disturbances. Curr Psychiatry Rep. 2009;11:459-465.
Young ME, Bray MS. Potential role for peripheral circadian clock dyssynchrony in the pathogenesis of cardiovascular dysfunction. Sleep Med. 2007;8:656-667.

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