title: Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, Guangdong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiren
authors.initials: W
authors.lastname: Dong
authors.forename: Suiqun
authors.initials: S
authors.lastname: Guo
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.forename: Suifen
authors.initials: S
authors.lastname: He
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhang
authors.forename: Yinjuan
authors.initials: Y
authors.lastname: Tang
authors.forename: Haihong
authors.initials: H
authors.lastname: Wang
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D016086:Lentivirus / Q000235:genetics; D009410:Nerve Degeneration / Q000209:etiology / Q000628:therapy*; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase