Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats

C. V. Borlongan, F. C. Zhou, T. Hayashi, T. P. Su, B. J. Hoffer, Y. Wang

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Exogenous application of transforming growth factors-β (TGFβ) family proteins, including glial cell line-derived neurotrophic factor (GDNF), neurturin, activin, and bone morphogenetic proteins, has been shown to protect neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effects for treatment of neurodegenerative diseases. Because fetal kidneys express many TGF/β trophic factors, we transplanted these tissues directly into the substantia nigra after a unilateral 6-hydroxydopamine lesion. We found that animals that received fetal kidney tissue grafts exhibited (1) significantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near normal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatum, (3) a preservation of K+-induced dopamine release in the lesioned striatum, and (4) high levels of GDNF protein within the grafts, in contrast, lesioned animals that received grafts of adult kidney tissues displayed significant behavioral deficits, dopaminergic depletion, reduced K+-mediated striatal dopamine release, and low levels of GDNF protein within the grafts. The present study suggests that fetal kidney tissue grafts can protect the nigrostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotrophic factors.

Original languageEnglish (US)
Pages (from-to)636-646
Number of pages11
JournalNeurobiology of Disease
Volume8
Issue number4
DOIs
StatePublished - Jan 1 2001

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Keywords

  • Dopamine
  • Glial cell line-derived neurotrophic factor
  • Motor asymmetry
  • Neural transplantation
  • Parkinson’s disease
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Neurology

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