title: Effects of age-related dopaminergic neuron loss in the substantia nigra on the circadian rhythms of locomotor activity in mice.
abstract: Elderly people often develop sleep and autonomic dysfunctions, which are regulated by circadian rhythm. Recently, we reported on the degradation of neural output from the central circadian clock in the suprachiasmatic nucleus (SCN) with aging. However, it is likely that many other factors contribute to the age-related decline in the functioning of the circadian system. In this study, we examined the effects of dopaminergic neuronal loss in the substantia nigra (SN) on circadian rhythms of mice to assess whether age-related degeneration of the dopamine system influences circadian rhythm. Young male C57BL/6J mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a compound that selectively destroys dopaminergic neurons in the SN, and their wheel-running activities were recorded. We observed that MPTP-treated mice lost 43% of their dopaminergic neurons in the SN (on average) and demonstrated longer period of wheel-running activity rhythm in constant darkness compared with control mice. However, all the remaining circadian parameters in the MPTP-treated mice remained constant. Our findings suggest that in addition to SCN output dysfunction, age-related degeneration in the dopamine system of the brain leads to circadian rhythm irregularities.
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo Heisei University, 4-1 Uruido-Minami, Ichihara, Chiba 290-0193, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.forename: Eriko
authors.initials: E
authors.lastname: Yamaguchi
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kana
authors.initials: K
authors.lastname: Hashimura
authors.forename: Takao
authors.initials: T
authors.lastname: Shibata
authors.forename: Wataru
authors.initials: W
authors.lastname: Nakamura
authors.forename: Takahiro J
authors.initials: TJ
authors.lastname: Nakamura
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000375:Aging / Q000473:pathology*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D009410:Nerve Degeneration / Q000139:chemically induced; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine