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Role of Rho-mediated ROCK-Semaphorin3A signaling pathway in the pathogenesis of Parkinson's disease in a mouse model

  • Author Footnotes
    1 Li Qi and Yong-Gang Tang are regarded as co-first authors.
    Li Qi
    Footnotes
    1 Li Qi and Yong-Gang Tang are regarded as co-first authors.
    Affiliations
    Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China
    Search for articles by this author
  • Author Footnotes
    1 Li Qi and Yong-Gang Tang are regarded as co-first authors.
    Yong-Gang Tang
    Footnotes
    1 Li Qi and Yong-Gang Tang are regarded as co-first authors.
    Affiliations
    Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China
    Search for articles by this author
  • Lin Wang
    Affiliations
    Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China
    Search for articles by this author
  • Wei He
    Affiliations
    Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China
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  • Hong-Hua Pan
    Affiliations
    Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China
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  • Rong-Rong Nie
    Correspondence
    Corresponding author at: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, No.1, Xinqiaoyuan Road, Xiangshan District, Guilin 541002, Guangxi Zhuang Autonomous Region, PR China.
    Affiliations
    Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China
    Search for articles by this author
  • Yan Can
    Affiliations
    Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China
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  • Author Footnotes
    1 Li Qi and Yong-Gang Tang are regarded as co-first authors.
Published:August 30, 2016DOI:https://doi.org/10.1016/j.jns.2016.08.061

      Highlights

      • Rho and ROCK knockout may reduce the damage by MPTP on mice behavior.
      • Rho and ROCK knockout protects dopaminergic neuron from injury.
      • Rho and ROCK knockout decreases Rho, ROCK, Sema3A and relevant factor mRNA expression.
      • Rho and ROCK knockout reduces Rho, ROCK, Sema3A and relevant factor proteins.
      • Rho and ROCK gene can serve as novel therapeutic targets of PD.

      Abstract

      Objective

      The present study aims to elucidate the role of Rho-mediated ROCK-Semaphorin3A signaling pathway in the pathogenesis of Parkinson's disease (PD) in a mouse model.

      Methods

      One-hundred twelve eight-week male C57BL/6 mice were selected. The mouse model of PD was constructed by intraperitoneal injection of MPTP. All mice were divided into four groups (28 mice in each group): Blank group, Model group, Rho knockout (Rho+/−) group and ROCK knockout (ROCK+/−) group. Changes of behavior of the mice were studied through automatic moving test and rotarod test. Immunohistochemistry (IHC) was used to detect the expressions of TH, CD11b and GFAP. High performance liquid chromatograph (HPLC) was performed for detection of dopamine and its metabolic product. The mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.

      Results

      Rho and ROCK knockout improved the damage caused by MPTP on the behavior of mice and protected dopaminergic neurons from injury, along with the increases of dopamine and its metabolic product. The mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were increased in PD mice in the Model group compared with those in the Blank group. Compared to the Model group, the mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were reduced in the Rho+/− and ROCK+/− groups.

      Conclusion

      These findings indicate that Rho and ROCK knockout may improve the behavior of mice and prevent MPTP-induced dopaminergic neurons damage by regulating Sema3A, PlexinA and NRP-1 in a mouse model of PD.

      Keywords

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