Abstract
Background Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder affecting 7–10 million individuals. The pathologic hallmark of PD is nigrostriatal dopaminergic neuron loss, leading to several motor and nonmotor disturbances, such as akinesia, gait disturbance, depression, and anxiety. Recent animal studies have demonstrated that physical exercise improves behavioral and neuropathological deficits in PD. However, the exact underlying mechanism underlying this effect remains unclear. In this study, we investigated whether long-term exercise has neuroprotective effects on dopaminergic nigrostriatal neurons and whether it further alleviates impairment of the gait pattern, locomotor activity, akinesia, and anxiety-like behavior in PD rats. Methods A hemiparkinsonian rat model, generated by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, was applied to evaluate neuroprotective effects and motor behaviors. Comprehensive spatiotemporal gait analysis, open-field locomotor activity, akinesia, apomorphine-induced rotational analysis, and dopaminergic neuron degeneration level were assessed every week and up to 8 weeks after daily voluntary running wheel exercise. Results Compared with the sham-treated group, we found that 10 weeks of voluntary exercise (i.e., 2-week exercise before PD lesion and 8-week exercise post-PD lesion) significantly reduced 6-OHDA-induced motor deficits in the gait pattern, akinesia, and rotational behavior in the exercise group. Immunohistochemically, a tyrosine hydroxylase-positive neuron in the substantia nigra was significantly preserved in the exercise group. Conclusions Our results demonstrated that long-term exercise training is effective for neuroprotection and further attenuates motor declines induced by 6-OHDA in an experimental model of PD. Our data further highlighted potential therapeutic effects of long-term physical exercise relevant to clinical effects for further potential application on human PD subjects.
Highlights
Parkinson’s disease (PD) is an idiopathic disease of the nervous system characterized by progressive tremor, bradykinesia, rigidity, and postural instability
The present study identified the therapeutic potential of long-term effects of early voluntary exercise intervention on a PD animal model by monitoring gait, locomotor activity, akinesia, and dopaminergic nigrostriatal neurons in 6-OHDA hemiparkinsonian rats as an early step toward possible eventual clinical conditions
The bar test is a useful indicator of akinesia, and twoway repeated measures analysis of variance (ANOVA) demonstrated significant main effects on the group (F = 64:143, p < 0:001), time course (F = 14:756, p < 0:001), and group vs. time interaction (F = 21:821, p < 0:001)
Summary
Parkinson’s disease (PD) is an idiopathic disease of the nervous system characterized by progressive tremor, bradykinesia, rigidity, and postural instability. Regarding nonmotor symptoms of PD, earlier research indicated that motor memory, cognitive ability, and daily activity can be improved after aerobic exercise training in individuals with PD [10, 14,15,16,17] These empirical data encourage exercise interventions for PD patients, epidemiological studies still cannot distinguish between beneficial impacts of exercise-induced neuroprotective effects on PD patients with and without appropriate exercise [18]. Previous prospective studies have been brief and underpowered, lacked proper controls, and failed to differentiate disease progression between short-term symptomatic improvement and long-term functional recovery in the PD population To overcome these difficulties in human studies, diseased animal models could provide a unique platform to eliminate theoretical discrepancy and clarify the necessary adjustments of an effective therapeutic strategy in understanding beneficial effects and related mechanisms of exercise training protocols and intervention. Our data further highlighted potential therapeutic effects of long-term physical exercise relevant to clinical effects for further potential application on human PD subjects
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