Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease

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• 作者：Yi Zhang (5)
  Weiren Dong (1)
  Suiqun Guo (5)
  Shu Zhao (1)
  Suifen He (2)
  Lihua Zhang (3)
  Yinjuan Tang (4)
  Haihong Wang (1)
  
• 关键词：N ; Terminal product of SHH ; Parkinson disease ; Neurogenesis ; Neuroregeneration
• 刊名：Neurological Sciences
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：35
• 期：12
• 页码：1931-1940
• 全文大小：3,447 KB
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• 作者单位：Yi Zhang (5)
  Weiren Dong (1)
  Suiqun Guo (5)
  Shu Zhao (1)
  Suifen He (2)
  Lihua Zhang (3)
  Yinjuan Tang (4)
  Haihong Wang (1)
  
  5. Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, Guangdong, China
  1. School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China
  2. Department of Laboratory, Shunde Guizhou Hospital, Foshan, 528305, Guangdong, China
  3. School of Medical Sciences, Foshan University, Foshan, 528000, Guangdong, China
  4. Department of Histology and Embryology, Xiangnan College, Chenzhou, 418000, Hunan, China
  
• ISSN：1590-3478

文摘

Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24?h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.