Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson's disease using GDNF

Exp Neurol. 2000 Jul;164(1):15-24. doi: 10.1006/exnr.2000.7409.


Local delivery of therapeutic molecules represents one of the limiting factors for the treatment of neurodegenerative disorders. In vivo gene transfer using viral vectors constitutes a powerful strategy to overcome this limitation. The aim of the present study was to validate the lentiviral vector as a gene delivery system in the mouse midbrain in the perspective of screening biotherapeutic molecules in mouse models of Parkinson's disease. A preliminary study with a LacZ-encoding vector injected above the substantia nigra of C57BL/6j mice indicated that lentiviral vectors can infect approximately 40,000 cells and diffuse over long distances. Based on these results, glial cell line-derived neurotrophic factor (GDNF) was assessed as a neuroprotective molecule in a 6-hydroxydopamine model of Parkinson's disease. Lentiviral vectors carrying the cDNA for GDNF or mutated GDNF were unilaterally injected above the substantia nigra of C57BL/6j mice. Two weeks later, the animals were lesioned ipsilaterally with 6-hydroxydopamine into the striatum. Apomorphine-induced rotation was significantly decreased in the GDNF-injected group compared to control animals. Moreover, GDNF efficiently protected 69.5% of the tyrosine hydroxylase-positive cells in the substantia nigra against 6-hydroxydopamine-induced toxicity compared to 33.1% with control mutated GDNF. These data indicate that lentiviral vectors constitute a powerful gene delivery system for the screening of therapeutic molecules in mouse models of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Cell Count / drug effects
  • Corpus Striatum / chemistry
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Dopamine / analysis
  • Genes, Reporter
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacology*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Lentivirus / genetics
  • Male
  • Mesencephalon / drug effects*
  • Mesencephalon / metabolism
  • Mesencephalon / pathology
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • Motor Activity / drug effects
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / administration & dosage
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Oxidopamine
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / pathology
  • Parkinson Disease, Secondary / therapy*
  • Substantia Nigra / chemistry
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Tyrosine 3-Monooxygenase / analysis


  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Apomorphine
  • Dopamine