Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice

Yun Hee Sung, Shin Chul Kim, Hoon Pyo Hong, Chang Youl Park, Mal Soon Shin, Chang Ju Kim, Jin Hee Seo, Dae Young Kim, Dong Je Kim, Han Jin Cho

    Research output: Contribution to journalArticlepeer-review

    97 Citations (Scopus)


    Aims: Parkinson's disease is a debilitating neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons. We investigated the effects of treadmill exercise on dopaminergic neuronal loss and microglial activation using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P)-induced Parkinson's disease mice. Main methods: Parkinson's disease was induced in mice by injection of MPTP/P. The mice in the exercise groups were put on a treadmill to run for 30 min/day, five times per week for four weeks. Motor balance and coordination was measured using rota-rod test. Expressions of inducible nitric oxide synthase (iNOS) and phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated NH2-terminal kinase (p-JNK), phosphorylated p-38 (p-p38), CD200, and CD200 receptor were determined by western blotting. Expressions of tyrosine hydroxylase (TH) and CD11b were evaluated by immunohistochemistry. Key findings: Parkinson's disease mice displayed poor motor balance and coordination with loss of nigrostriatal dopaminergic neurons. iNOS expression was enhanced via up-regulation of phosphorylated mitogen-activated protein kinases (p-MAPKs) signaling, such as p-ERK, p-JNK, and p-p-38 in the Parkinson's disease mice. Microglial activation was also observed in the Parkinson's disease mice, showing increased CD11b expression with suppressed CD200 and CD200 receptor expressions. Treadmill exercise prevented the loss of nigrostriatal dopaminergic neurons, and ameliorated the motor balance and coordination dysfunction in the Parkinson's disease mice. Treadmill exercise suppressed iNOS expression via down-regulation of MAPKs and also inhibited microglial activation in the Parkinson's disease mice. Significance: Treadmill exercise prevented dopaminergic neuronal loss by inhibiting brain inflammation through suppression of microglial activation in the Parkinson's disease mice.

    Original languageEnglish
    Pages (from-to)1309-1316
    Number of pages8
    JournalLife Sciences
    Issue number25-26
    Publication statusPublished - 2012 Dec 17

    Bibliographical note

    Funding Information:
    This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST) ( NRF-2010-0022895 ).


    • CD11b
    • CD200
    • Exercise
    • MAPKs signaling
    • MPTP
    • Parkinson's disease

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology
    • Pharmacology, Toxicology and Pharmaceutics(all)


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