Alteration of Biological Rhythms in Diseases of the Central Dopaminergic System: Focus on Parkinson’s Disease

Abstract

Parkinson’s Disease (PD) is characterized by profound alterations of the circadian timing system, as evidenced by studies in animals and patients. Alterations in activity, temperature and heart rate rhythms have been observed in several animal models of PD. Deposition of alpha-synuclein in the hypothalamic suprachiasmatic nuclei (SCN) (i.e, the site of central oscillator) has been detected in transgenic mice and altered rhythms in clock genes have been reported in both the striatum and the SCN. Furthermore, enucleation of the lateral hypothalamus, leading to “functional blindness” aggravated parkinsonian symptoms in one PD animal model. Disturbances in biological rhythms have also been observed in PD patients. Of note, polymorphisms of the ARNTL and PER1 clock genes were more frequent in PD patients compared to controls. Together with the extensive cross-talk between the basal ganglia and SCN, these pieces of evidence suggest that disturbances in the circadian timing system might be part of the core features of PD and not just a “collateral damage”. According to this view, a disturbed clockwork might actively contribute to neurodegeneration and a chronotherapeutic approach to PD might be considered. Melatonin, as a prototype chronobiotic agent, has been shown to have some efficacy for sleep disorder treatment in PD and exhibit neuroprotection in animal models of PD. Bright light has also been effective for depression and insomnia in PD patients. Novel chronobiological therapies might have a great impact on the clinical management of PD.