Effects of Preventive Treadmill Exercise on the Recovery of Metabolic and Mitochondrial Factors in the 6-Hydroxydopamine Rat Model of Parkinson's Disease

Abstract

Metabolic and mitochondrial dysfunction has been implicated in Parkinson's disease, while exercise can induce essential pathways of mitochondrial biogenesis. Here, we tested whether long-term preventive treadmill training (16 weeks, 21 m/min, and 0 degrees inclinations for 50 min/d, 5 d/week) effects the mitochondrial and neurodegeneration markers, in the striatum of rats in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Following 16 weeks of exercise or no exercise period (n = 16 rats per group), the animals were divided into four experimental groups (n = 8 per group): (1) no exercise and saline (SED), (2) exercise and saline (EX), (3) no exercise and 6-OHDA (SED + 6-OHDA), and (4) exercise and 6-OHDA (EX + 6-OHDA). For the model, 8 mu g of 6-OHDA (2 mu g/mu L prepared in a solution of 0.2 ascorbic acid and 0.9 saline) was injected into the right medial forebrain bundle. Exposure to 6-OHDA resulted in a significant reduction (P < 0.05) of mitochondrial factors AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma coactivator-1 alpha, and tyrosine hydroxylase, and increased expression of silent information regulator T1, mitochondrial transcription factor A, and p53 in the SED + 6-OHDA group relative to SED group. By contrast, gene and protein expressions upon exercise were higher and p53 protein level was lower in the EX + 6-OHDA group compared with SED + 6-OHDA. Further, exercise reduced the extent of weight loss associated with the 6-OHDA injection. In conclusion, exercise might be used to reduce mitochondrial disorders in Parkinson's disease.