A New Perspective for Parkinson's Disease: Circadian Rhythm

Abstract

Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

Keywords: Circadian rhythm; Dopamine; Parkinson’s disease; Sleep.

Fig. 1

A simplified scheme of the disturbed circadian system in PD. Reduced time cues are obtained from external zeitgebers in PD patients, due to the impaired visual acuity and disabled motor ability. Meanwhile, the internal circadian clock outputs are damaged in SCN, where the α-synuclein is accumulated. As a result, disrupted rhythm of clock genes in SCN impairs its modulation of other central and peripheral clocks, which might have negative consequences on behavioral and physiological functions. SCN, suprachiasmatic nuclei; SN, substantia nigra.