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Molecular Neurobiology

, Volume 53, Issue 4, pp 2258–2268 | Cite as

Treatment with Trehalose Prevents Behavioral and Neurochemical Deficits Produced in an AAV α-Synuclein Rat Model of Parkinson’s Disease

  • Qing He
  • James B. Koprich
  • Ying Wang
  • Wen-bo Yu
  • Bao-guo Xiao
  • Jonathan M. BrotchieEmail author
  • Jian WangEmail author
Article

Abstract

The accumulation of misfolded α-synuclein in dopamine (DA) neurons is believed to be of major importance in the pathogenesis of Parkinson’s disease (PD). Animal models of PD, based on viral-vector-mediated over-expression of α-synuclein, have been developed and show evidence of dopaminergic toxicity, providing us a good tool to investigate potential therapies to interfere with α-synuclein-mediated pathology. An efficient disease-modifying therapeutic molecule should be able to interfere with the neurotoxicity of α-synuclein aggregation. Our study highlighted the ability of an autophagy enhancer, trehalose (at concentrations of 5 and 2 % in drinking water), to protect against A53T α-synuclein-mediated DA degeneration in an adeno-associated virus serotype 1/2 (AAV1/2)-based rat model of PD. Behavioral tests and neurochemical analysis demonstrated a significant attenuation in α-synuclein-mediated deficits in motor asymmetry and DA neurodegeneration including impaired DA neuronal survival and DA turnover, as well as α-synuclein accumulation and aggregation in the nigrostriatal system by commencing 5 and 2 % trehalose at the same time as delivery of AAV. Trehalose (0.5 %) was ineffective on the above behavioral and neurochemical deficits. Further investigation showed that trehalose enhanced autophagy in the striatum by increasing formation of LC3-II. This study supports the concept of using trehalose as a novel therapeutic strategy that might prevent/reverse α-synuclein aggregation for the treatment of PD.

Keywords

Parkinson’s disease α-Synuclein Trehalose DA Autophagy 

Notes

Acknowledgments

This work was supported by grants from the National Foundation of Natural Science of China (No.81071018 and No.81371413), key project from Science and Technology Commission of Shanghai Municipality (13JC1401103), and project of Shanghai Municipal Commission of Health (XBR2013088). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Shun Yu from Xuanwu Hospital of the Capital University of Medical Sciences, Beijing, China, for kindly providing the human α-synuclein antibody for immunofluorescence.

Conflict of interest

The authors declare that they have no competing interests.

Authors’ contributions

WJ, Koprich JB, and Brotchie JM designed this study. HQ, WY, and YWB performed this study, analyzed data, and wrote the manuscript. XBG assisted in behavioral analysis. All authors discussed the results and provided comments on the manuscript. All authors read and approved the final manuscript.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Qing He
    • 1
    • 3
  • James B. Koprich
    • 2
  • Ying Wang
    • 1
  • Wen-bo Yu
    • 1
  • Bao-guo Xiao
    • 1
  • Jonathan M. Brotchie
    • 2
    Email author
  • Jian Wang
    • 1
    Email author
  1. 1.Department & Institute of Neurology, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.Toronto Western Research Institute, Toronto Western HospitalUniversity Health NetworkTorontoCanada
  3. 3.Department of Neurology, Shanghai Ninth People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina

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