Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkin
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(2020) 16:9 Monir et al. Behav Brain Funct https://doi.org/10.1186/s12993-020-00171-9
Open Access
RESEARCH
Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkinson’s disease in rotenone‑treated rats Dina M. Monir1†, Motamed E. Mahmoud2*†, Omyma G. Ahmed3, Ibrahim F. Rehan4 and Amany Abdelrahman1*
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. Keywords: Parkinson, Rotenone, Behavioral tests, Exercise, Nrf2. TFAM, Noq1
*Correspondence: [email protected]; amany_abdelhameed@med. sohag.edu.eg † Dina M. Monir and Motamed E. Mahmoud are equally contributed 1 Department of Physiology, Faculty of Medicine, Sohag University, Sohag 82524, Egypt 2 Department of Animal Behavior and Husbandry (Genetics, Breeding, and Production), Faculty of Veterinary Medicine, Sohag University, Sohag 82524, Egypt Full list of author information is available at the end of the article
Background Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by persistent loss of nigrostriatal dopaminergic neurons leading to depletion of dopamine and consequent problems of movement, emotions, and cognition. While many factors contribute to the pathogenesis of PD, damage of dopaminergic neurons by oxygen-derived free radicals is considered an important
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