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

SANTIAGO PEREZ LLORET; DARIO ACUÑA-CASTROVIEJO; VICTOR DEMARIA-PESCE; DANIEL CARDINALI

Dopamine and Sleep

Springer

Año: 2016; p. 91 - 115

Parkinson?s Disease (PD) is characterized by profound alterations of the circadian timing system, asevidenced by studies in animals and patients. Alterations in activity, temperature and heart rate rhythmshave been observed in several animal models of PD. Deposition of alpha-synuclein in the hypothalamicsuprachiasmatic nuclei (SCN) (i.e, the site of central oscillator) has been detected in transgenic mice andaltered 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 parkinsoniansymptoms in one PD animal model. Disturbances in biological rhythms have also been observed in PDpatients. Of note, polymorphisms of the ARNTL and PER1 clock genes were more frequent in PD patientscompared to controls. Together with the extensive cross-talk between the basal ganglia and SCN, thesepieces of evidence suggest that disturbances in the circadian timing system might be part of the corefeatures of PD and not just a ?collateral damage?. According to this view, a disturbed clockwork mightactively 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 disordertreatment in PD and exhibit neuroprotection in animal models of PD. Bright light has also been effectivefor depression and insomnia in PD patients. Novel chronobiological therapies might have a great impact onthe clinical management of PD.