GDNF partially protects grafted fetal dopaminergic neurons against 6-hydroxydopamine neurotoxicity

David M. Yurek, Anita Fletcher-Turner

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Rats were given unilateral 6-hydroxydopamine (6-OHDA) lesions and subsequently received transplants of fetal ventral mesencephalic tissue into the denervated striatum. Four weeks later transplanted animals were tested for graft-mediated reduction of amphetamine-induced rotational behavior. Subsequently, transplanted animals received an intrastriatal injection of either GDNF (10 μg) or citrate buffer into a site lateral to the transplant, and then 6 h later received an injection of either 4.0 μg of 6-OHDA, 8.0 μg of 6-OHDA, or vehicle using the same stereotaxic coordinates that were used for the GDNF/citrate buffer injection. Animals were re-tested for amphetamine-induced rotational behavior 2 weeks later. Histological analysis revealed a significant reduction in the number of cell bodies immunostained for tyrosine hydroxylase (TH+) within the transplant for those animals pretreated with an intrastriatal injection of citrate buffer and subsequently given either dose of 6-OHDA. Transplanted animals pretreated with GDNF and subsequently administered 8.0 μg of 6-OHDA showed a significant reduction of TH+ neurons within the transplant compared to controls, however TH+ cell counts for this group remained significantly higher than the TH+ cell counts for the group of animals receiving the same dose of 6-OHDA but pretreated with citrate buffer. GDNF pretreatment completely protected TH+ cell bodies against 4.0 μg of 6-OHDA. Rotational scores indicated that GDNF provided only partial protection against 6-OHDA neurotoxicity in terms of transplant function. For both groups of transplanted animals receiving GDNF pretreatment and 6-OHDA injections, amphetamine-induced rotational scores dropped below the scores for animals pretreated with citrate buffer but remained significantly higher than the scores for transplanted animals that were not injected with 6-OHDA. Both histological and behavioral measures indicate GDNF partially protects integrated transplants against neurotoxic insult. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalBrain Research
Issue number1
StatePublished - Oct 16 1999

Bibliographical note

Funding Information:
This research was supported by NS35890 and the generous gift of GDNF from Amgen.


  • Glial cell line-derived neurotrophic factor
  • Neural transplantation
  • Neuroprotection
  • Neurotrophic factor
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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