Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons

J Comp Neurol. 1995 May 15;355(4):479-89. doi: 10.1002/cne.903550402.


Glial cell-lined derived neurotrophic factor (GDNF) has been shown to promote survival of developing mesencephalic dopaminergic neurons in vitro. In order to determine if there is a positive effect of GDNF on injured adult midbrain dopaminergic neurons in situ, we have carried out experiments in which a single dose of GDNF was injected into the substantia nigra following a unilateral lesion of the nigrostriatal system. Rats were unilaterally lesioned by a single stereotaxic injection of 6-hydroxydopamine (6-OHDA; 9 micrograms/4 microliters normal saline with 0.02% ascorbate) into the medial forebrain bundle and tested weekly for apomorphine-induced (0.05 mg/kg s.c.) contralateral rotation behavior. Rats that manifested > 300 turns/hour received a nigral injection of 100 micrograms GDNF, or cytochrome C as a control, 4 weeks following the 6-OHDA lesion. Rotation behavior was quantified weekly for 5 weeks after GDNF. Rats were subsequently anesthetized, transcardially perfused, and processed for tyrosine hydroxylase immunohistochemistry. It was found that 100 micrograms GDNF decreased apomorphine-induced rotational behavior by more than 85%. Immunohistochemical studies revealed that tyrosine hydroxylase immunoreactivity was equally reduced in the striatum ipsilateral to the lesion in both cytochrome C and GDNF-injected animals. In contrast, large increments in tyrosine hydroxylase immunoreactivity were observed in the substantia nigra of animals treated with 100 micrograms of GDNF, with a significant increase in numbers of tyrosine hydroxylase-immunoreactive cell bodies and neurites as well as a small increase in the cell body area of these neurons. The results suggest that GDNF can maintain the dopaminergic neuronal phenotype in a number of nigral neurons following a unilateral nigrostriatal lesion in the rat.

MeSH terms

  • Animals
  • Apomorphine
  • Cell Survival / drug effects
  • Dopamine / physiology*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Male
  • Mesencephalon / anatomy & histology
  • Mesencephalon / cytology*
  • Mesencephalon / drug effects
  • Nerve Growth Factors / administration & dosage
  • Nerve Growth Factors / pharmacology*
  • Nerve Tissue Proteins / administration & dosage
  • Nerve Tissue Proteins / pharmacology*
  • Neuronal Plasticity / drug effects
  • Neurons / drug effects*
  • Oxidopamine
  • Rats
  • Rats, Inbred F344
  • Stereotyped Behavior / drug effects
  • Tyrosine 3-Monooxygenase / metabolism


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