title: Lack of long-term changes in circadian, locomotor, and cognitive functions in acute and chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse models of Parkinson's disease.
abstract: In addition to the hallmark motor disorders in Parkinson's disease (PD) patients, nonmotor symptoms have attracted increasing attention. Among the nonmotor symptoms, sleep disturbances and cognitive deficits are frequently reported and contribute to a decrease in the quality of life. The pathophysiology of cognitive and sleep-wake abnormalities in PD is poorly understood partially due to the lack of appropriate animal models that fully replicate the entire pathological and behavioral spectrum of the disease. In this study, we undertook a long-term evaluation of circadian, locomotor and cognitive abilities in both acute and chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mouse models. Activity rhythms and locomotor activity were assayed under light-dark cycles, constant darkness, or constant light, re-entrainment to shifts of the light-dark cycle, and a behavioral masking paradigm. Cognitive abilities were assessed using a radial water maze task. Although both acute and chronic treatment regimes induced 70% degeneration of dopaminergic neurons in the substantia nigra, neither circadian nor cognitive alterations were observed even after nearly 1 yr. During aging, there was a significant decrease of locomotor activity and of several circadian parameters without any exacerbation in MPTP-treated animals. These results emphasize the limitations of the MPTP-treated mouse as an animal model of nonmotor symptoms of PD in addition to the already well-documented inadequacy to replicate cardinal motor features of the disease.
authors.affiliation: Department of Chronobiology, Inserm U846, Stem Cell and Brain Research Institute, Bron, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fifel
authors.forename: Ouria
authors.initials: O
authors.lastname: Dkhissi-Benyahya
authors.forename: Howard M
authors.initials: HM
authors.lastname: Cooper
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000008:administration & dosage; D007858:Learning / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase