Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkinson's disease in rotenone-treated rats

Abstract

Background Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of nigrostriatal dopaminergic neurons leading to dopamine depletion and problems of movement, emotions, and cognition. While the pathogenesis of PD is not clear, damage of dopaminergic neurons by oxygen-derived free radicals is considered an important contributing mechanism. This study aimed to evaluate the role of treadmill exercise in male Wister rats as a single treatment and as an aid-therapy with L-dopa for rotenone-induced PD. To study the role of the Nrf2- ARE pathway as a mechanism involved in exercise-associated improvement in rotenone-induced PD in rats. Method Animals were divided into 5 groups, (Control, rotenone, rotenone\exercise, rotenone\L-dopa, and rotenone\exercise\L-dopa (combination)groups). After the PD induction, rats in the rotenone\exercise and combination groups were daily treadmill exercised for 4 weeks. Results Treadmill exercise significantly improved behavioral and motor aspects of rotenone-induced PD. When treadmill exercise was introduced as a single intervention, it amended most behavioral aspects of PD, gait fully corrected, short-term memory, and motor coordination. Where L-dopa corrected locomotor activity and motor coordination but failed to improve short-term memory and only partially corrected the gait of rotenone-treated rats. When treadmill exercise was combined with L-dopa, all features of PD were corrected. It was found that exercise upregulated some of its associative genes to Nrf2 pathways such as TFAM, Nrf2 and NQO.1 mRNA expression. Conclusion This study suggests that forced exercise improved parkinsonian like features by activating the Nrf2 pathway.

HR LC-MS/MS metabolomic profiling of Yucca aloifolia fruit and the potential neuroprotective effect on rotenone-induced Parkinson’s disease in rats

“…The mean latency evidenced motor abnormalities associated with PD to fall time, latency to move, several crossed squares, latency to the rear, and several rears performed in rotarod and open field testing, all of which showed poor performance of the rotenone group. In contrast, depressive behavior associated with PD was manifested in the rotenone group as decreased swimming and climbing time and increased immobility time through the forced swim test, confirmed by previous literature reports [ 2 , 45 , 46 ].…”

The Impact of Resistance Training With Coenzyme Q10 Supplementation on Antioxidant Value of Nuclear Factor-Erythroid-2-Related Factor 2 in Young Male Rats

“…In the lack of Keap1, Nrf2 is transported toward the hmj.hums.ac.ir http core, sticks to ARE, and expresses Nrf2 genes, including NQO1 and other genes such as glutamate, cysteine ligase, and glutathione (28). Exercise activity along with Q10 supplementation showed that Nrf2, an antioxidant protein mainly produced by ROS, increased during exercise (29). According to our results, exercise stimulates Nrf2 and NQO1 transcription factors, reduces oxidative stress, and enhances antioxidant defense (30).…”

Effects of curcumin, quercetin, and their combinationson neurodegeneration and motor impairment in rotenone-induced Parkinson's disease in rats

“…The apparatus consists of a runway of 50-60 cm. The paws of each rat were painted with non-toxic paint then rats were allowed to walk on the narrow runway on which white paper was placed to take the footprints [41,42]. The test period was videotaped.…”