title: Circadian rhythm dysfunction: a novel environmental risk factor for Parkinson's disease.
abstract: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Although rare genetically linked cases of PD have been reported, most incidences are sporadic in nature. Late-onset, sporadic PD is thought to result from the combined effects of genetic and environmental risk factors exposure. Sleep and circadian rhythm disorders are recurrent among PD patients and appear early in the disease. Although some evidence supports a relationship between circadian disruption (CD) and PD, whether this is secondary to the motor symptoms or, indeed, is a factor that contributes to the pathogenesis of the disease remains to be investigated. In the present paper, we studied the direct consequence of chronic CD on the development of the phenotype in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinen) model of PD. Pre-exposure to CD to mice treated with MPTP resulted in an exacerbation of motor deficit and a significant reduction in the capability of acquiring motor skills. These changes were associated with a greater loss of tyrosine hydroxylase cell content and intense neuroinflammation. Taken together, our findings demonstrate that CD by triggering a robust neuroinflammatory reaction and degeneration of the nigral-dopaminergic neuronal system exacerbates motor deficit. They support the novel hypothesis that circadian rhythm disorder is an environmental risk factor for developing PD.
authors.affiliation: Department of Pharmacology, Center for Translational Medicine, School of Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Lauretti
authors.affiliation: Department of Pharmacology, Center for Translational Medicine, School of Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Di Meco
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Merali
authors.affiliation: Department of Pharmacology, Center for Translational Medicine, School of Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Praticò
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D021081:Chronobiology Disorders / Q000150:complications*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D012307:Risk Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase