Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo

Neurosci Lett. 1994 Nov 21;182(1):107-11. doi: 10.1016/0304-3940(94)90218-6.


Fischer 344 rats were unilaterally injected into the medial forebrain bundle with 6-hydroxydopamine (6-OHDA). Apomorphine-induced rotational behavior was used to select animals whose rotation exceeded 300 turns/h, corresponding to greater than 95% dopamine (DA) depletion in the ipsilateral striatum. Four weeks later, glial cell line-derived neurotrophic factor (GDNF) or vehicle was injected intranigrally ipsilateral to the lesion (0.1-100 micrograms). The highest dose of GDNF tested produced a marked decrease in rotational behavior. This dose also produced levels of DA in the ipsilateral substantia nigra (SN) which were not statistically different from the contralateral side. Vehicle-treated animals showed a marked DA depletion in the ipsilateral SN. These results demonstrate neurochemical and behavioral improvements in unilaterally DA-lesioned rats following intranigral administration of GDNF, suggesting that GDNF may develop into a useful therapy for Parkinson's disease.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cell Line
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Injections
  • Male
  • Mesencephalon / drug effects*
  • Mesencephalon / pathology
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / pharmacology*
  • Neuroglia / metabolism*
  • Neurons / drug effects*
  • Oxidopamine / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Rotation
  • Stereotyped Behavior / drug effects
  • Substantia Nigra / physiology


  • Nerve Growth Factors
  • Oxidopamine
  • Dopamine