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

Marandi, S.M and Esfarjani, F and Feyzollahzadeh, S and Alaei, H and Rezaee, Z (2019) Effects of Preventive Treadmill Exercise on the Recovery of Metabolic and Mitochondrial Factors in the 6-Hydroxydopamine Rat Model of Parkinson’s Disease. Neurotoxicity Research. pp. 1-10.

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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° 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’sdisease.Following16weeksofexerciseornoexerciseperiod(n =16rats 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 μgof6-OHDA(2μg/μL 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’sdisease.

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