Abstract
Exercise has been recommended to improve motor function in Parkinson patients, but its value in altering progression of disease is unknown. In this study, we examined the neuroprotective effects of running wheel exercise in mice. In adult wild-type mice, one week of running wheel activity led to significantly increased DJ-1 protein concentrations in muscle and plasma. In DJ-1 knockout mice, running wheel performance was much slower and Rotarod performance was reduced, suggesting that DJ-1 protein is required for normal motor activity. To see if exercise can prevent abnormal protein deposition and behavioral decline in transgenic animals expressing a mutant human form of α-synuclein in all neurons, we set up running wheels in the cages of pre-symptomatic animals at 12 months old. Activity was monitored for a 3-month period. After 3 months, motor and cognitive performance on the Rotarod and Morris Water Maze were significantly better in running animals compared to control transgenic animals with locked running wheels. Biochemical analysis revealed that running mice had significantly higher DJ-1, Hsp70 and BDNF concentrations and had significantly less α-synuclein aggregation in brain compared to control mice. By contrast, plasma concentrations of α-synuclein were significantly higher in exercising mice compared to control mice. Our results suggest that exercise may slow the progression of Parkinson’s disease by preventing abnormal protein aggregation in brain.
Highlights
Parkinson’s disease is characterized by the loss of midbrain dopamine neurons in the substantia nigra pars compacta [1, 2]
Since we have previously reported that higher DJ-1 levels in brain are associated with reduced α-synuclein aggregation, we examined DJ-1 levels in mouse tissues and plasma after exercise
Using Western blots and ELISA assays, we found that running mice had significantly higher DJ-1 levels in muscle (Fig 1A, ÃÃp
Summary
Parkinson’s disease is characterized by the loss of midbrain dopamine neurons in the substantia nigra pars compacta [1, 2]. Death of dopamine neurons has been attributed to oxidative stress, abnormal protein aggregation, and genetic factors [3,4,5]. Mutations in many genes have been linked to Parkinson’s including α-synuclein, Parkin, UCHL1, DJ-1, PINK1, LRRK2, and VSP35 [6,7,8]. The gene mutations could lead to either loss of neuroprotective functions such as DJ-1 and PINK1, or gain of toxic functions such as α-synuclein and LRRK2 [9]. Single amino acid mutations in the α-synuclein gene as well as simple triplication of the gene have been shown to cause autosomal-dominant forms of Parkinson’s disease [10, 11].
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