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Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector.

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Author

Summary, in English

We used a recombinant lentiviral vector (rLV) for gene delivery of GDNF to the striatum, and assessed its neuroprotective effects in the intrastriatal 6-hydroxydopamine (6-OHDA) lesion model.The level of GDNF expression obtained with the rLV-GDNF vector was dose-related and ranged between 0.9-9.3 ng/mg tissue in the transduced striatum, as determined by ELISA, and 0.2-3.0 ng/mg tissue were detected in the ipsilateral substantia nigra (SN), due to anterograde transport of the GDNF protein. GDNF expression was apparent at 4 days and maintained for > 8 months after injection. Striatal delivery of rLV-GDNF efficiently protected the nigral dopamine (DA) neurons and their projection, against the 6-OHDA lesion (65-77% of intact side). Sprouting of the lesioned axons was observed along the nigrostriatal pathway, precisely corresponding to the areas containing anterogradely transported GDNF.

Department/s

Publishing year

2002

Language

English

Pages

75-82

Publication/Series

NeuroReport

Volume

13

Issue

1

Document type

Journal article

Publisher

Lippincott Williams & Wilkins

Topic

  • Neurosciences

Keywords

  • Lentivirus : genetics
  • Luminescent Proteins : pharmacokinetics
  • Motor Activity : drug effects
  • Nerve Tissue Proteins : genetics
  • Nerve Tissue Proteins : pharmacokinetics
  • Nerve Tissue Proteins : therapeutic use
  • Neurons : drug effects
  • Neurons : metabolism
  • Neuroprotective Agents : therapeutic use
  • Oxidopamine : pharmacology
  • Parkinson Disease : pathology
  • Parkinson Disease : physiopathology
  • Parkinson Disease : therapy
  • Rats
  • Sprague-Dawley
  • Substantia Nigra : drug effects
  • Substantia Nigra : pathology
  • Support
  • Non-U.S. Gov't
  • Tyrosine 3-Monooxygenase : metabolism
  • Indicators and Reagents : pharmacokinetics
  • Genetic Vectors
  • Gene Transfer Techniques
  • Female
  • Dopamine : metabolism
  • Corpus Striatum : pathology
  • Corpus Striatum : drug effects
  • Animal

Status

Published

Research group

  • Neurobiology

ISBN/ISSN/Other

  • ISSN: 1473-558X