Bright light improves sleep in patients with Parkinson\u2019s disease: possible role of circadian restoration

Takuyuki Endo,Yasufumi Shigeyoshi,Saburo Sakoda,Makoto Akashi,Tomoko Yoshikawa,Ritsuko Matsumura,Isao T Tokuda,Koichi Node

doi:10.1038/s41598-020-64645-6

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. Among the most common manifestations of PD are sleep problems, which are coupled with the adverse effects of dopaminergic therapies (DT). A non-pharmacological solution for these sleep problems has been sought to avoid additional pharmacological intervention. Here, we show that bright light therapy (BLT) is effective for improving sleep in Japanese PD patients receiving DT. Furthermore, experimental evaluation of peripheral clock gene expression rhythms revealed that most PD patients receiving DT who experienced improved sleep following BLT showed a circadian phase shift, indicating the existence of a correlation between circadian modulation and sleep improvement. Conversely, this result indicates that sleep problems in PD patients receiving DT may arise at least in part as a result of circadian dysfunction. Indeed, we found that chronic dopaminergic stimulation induced a rapid attenuation of autonomous oscillations of clock gene expression in ex vivo cultured mouse suprachiasmatic nucleus (SCN) at the single neuron level. In conclusion, BLT is a promising medical treatment for improving sleep in PD patients receiving DT. This BLT-induced improvement may be due to the restoration of circadian function.

Highlights

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders
We investigated the effect of bright light therapy (BLT) on sleep problems in East Asian (Japanese) PD patients
Re-examination of these scales after the period of bright light exposure revealed no significant change in the Unified Parkinson’s Disease Rating Scale (UPDRS) part III or Epworth Sleepiness Scale (ESS) scores but showed a significant positive impact on sleep according to the Parkinson Disease Sleep Scale 2 (PDSS-2) score (Table 2)

Summary

Introduction

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. Among the most common manifestations of PD are sleep problems, which are coupled with the adverse effects of dopaminergic therapies (DT). In further support for these human studies, animal studies have demonstrated that dopamine receptors expressed in the SCN play a role in a photic input pathway to modulate suprachiasmatic circadian function[19,20] This infers that chronic exposure of the SCN to excess dopamine and its derivatives causes some functional impairment of the SCN, in turn leading to the speculation that DT-induced functional impairment of the suprachiasmatic clock causes sleep problems in DT-receiving PD patients. We aimed to provide further evidence on whether BLT-mediated sleep improvement in DT-receiving PD patients involves functional modulation of the central circadian clock, and whether DT-induced suprachiasmatic dysfunction is a cause of sleep problems in these patients. To obtain evidence on the negative effects of chronic dopamine exposure on the suprachiasmatic function, we performed ex vivo culture of mouse SCN and real-time monitoring of clock gene expression rhythms under chronic treatment with dopamine

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