Effects of age-related dopaminergic neuron loss in the substantia nigra on the circadian rhythms of locomotor activity in mice

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.

► We examined effects of dopamine system degeneration on circadian rhythmicity.
► MPTP lengthens the circadian period of locomotor activity.
► Age-related degeneration of the dopamine system may alter the circadian cycle.