Glial cell line-derived neurotrophic factor improves survival of ventral mesencephalic grafts to the 6-hydroxydopamine lesioned striatum

A. C. Granholm, J. L. Mott, K. Bowenkamp, S. Eken, S. Henry, B. J. Hoffer, P. A. Lapchak, M. R. Palmer, C. Van Horne, G. A. Gerhardt

Research output: Contribution to journalArticle

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Abstract

One approach to replace lost dopaminergic neurons in Parkinson's disease is to transplant fetal mesencephalic tissue into the striatum. In an attempt to expand the developmental window useful for grafting of mesencephalic tissue and increase the fiber outgrowth from grafted dopaminergic neurons, we have pretreated fetal mesencephalic tissue with the dopaminotrophic factor glial cell line-derived neurotrophic factor (GDNF). Mesencephalic tissue pieces from embryonic day 18-19 Fischer 344 rats were preincubated for 20 min with GDNF (1 μg/μl) or vehicle. Two tissue pieces were then transplanted into the striatum of rats that had been unilaterally lesioned by medial forebrain bundle injections of 6-hydroxydopamine. The animals were tested for apomorphine-induced rotations prior to intracranial grafting. Host rats received intrastriatal injections of 10 μg GDNF or control solution at 10 days and 4 weeks postgrafting. The animals were tested in the rotometer twice monthly following transplantation. Despite the fact that these transplants were from a suboptimal donor stage, the rotations were significantly decreased in both transplanted groups. Immunohistochemical evaluation of the host brains revealed that the overall size of transplanted mesencephalic tissue was significantly increased in the GDNF-treated animals, and that the average size of transplanted tyrosine hydroxylase (TH)-positive neurons was also increased. Furthermore, we found that the innervation density of surrounding host striatal tissue was significantly increased in the GDNF-treated group, as compared with controls. Taken together, these results suggest that treatment of intrastriatal ventral mesencephalon grafts with GDNF can optimize the conditions for intracranial grafting and thus improve the chances for functional recovery following the intrastriatal grafting procedure.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalExperimental Brain Research
Volume116
Issue number1
DOIs
StatePublished - Sep 8 1997

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Oxidopamine
Transplants
Dopaminergic Neurons
Fetus
Medial Forebrain Bundle
Corpus Striatum
Tissue Transplantation
Injections
Apomorphine
Inbred F344 Rats
Tyrosine 3-Monooxygenase
Mesencephalon
Parkinson Disease
Transplantation
Neurons
Brain

Keywords

  • Glial cell line-derived neurotrophic factor
  • Neurotrophic factors
  • Nigrostriatal dopaminergic pathway
  • Striatum
  • Transplants

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Glial cell line-derived neurotrophic factor improves survival of ventral mesencephalic grafts to the 6-hydroxydopamine lesioned striatum. / Granholm, A. C.; Mott, J. L.; Bowenkamp, K.; Eken, S.; Henry, S.; Hoffer, B. J.; Lapchak, P. A.; Palmer, M. R.; Van Horne, C.; Gerhardt, G. A.

In: Experimental Brain Research, Vol. 116, No. 1, 08.09.1997, p. 29-38.

Research output: Contribution to journalArticle

Granholm, AC, Mott, JL, Bowenkamp, K, Eken, S, Henry, S, Hoffer, BJ, Lapchak, PA, Palmer, MR, Van Horne, C & Gerhardt, GA 1997, 'Glial cell line-derived neurotrophic factor improves survival of ventral mesencephalic grafts to the 6-hydroxydopamine lesioned striatum', Experimental Brain Research, vol. 116, no. 1, pp. 29-38. https://doi.org/10.1007/PL00005741
Granholm, A. C. ; Mott, J. L. ; Bowenkamp, K. ; Eken, S. ; Henry, S. ; Hoffer, B. J. ; Lapchak, P. A. ; Palmer, M. R. ; Van Horne, C. ; Gerhardt, G. A. / Glial cell line-derived neurotrophic factor improves survival of ventral mesencephalic grafts to the 6-hydroxydopamine lesioned striatum. In: Experimental Brain Research. 1997 ; Vol. 116, No. 1. pp. 29-38.
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abstract = "One approach to replace lost dopaminergic neurons in Parkinson's disease is to transplant fetal mesencephalic tissue into the striatum. In an attempt to expand the developmental window useful for grafting of mesencephalic tissue and increase the fiber outgrowth from grafted dopaminergic neurons, we have pretreated fetal mesencephalic tissue with the dopaminotrophic factor glial cell line-derived neurotrophic factor (GDNF). Mesencephalic tissue pieces from embryonic day 18-19 Fischer 344 rats were preincubated for 20 min with GDNF (1 μg/μl) or vehicle. Two tissue pieces were then transplanted into the striatum of rats that had been unilaterally lesioned by medial forebrain bundle injections of 6-hydroxydopamine. The animals were tested for apomorphine-induced rotations prior to intracranial grafting. Host rats received intrastriatal injections of 10 μg GDNF or control solution at 10 days and 4 weeks postgrafting. The animals were tested in the rotometer twice monthly following transplantation. Despite the fact that these transplants were from a suboptimal donor stage, the rotations were significantly decreased in both transplanted groups. Immunohistochemical evaluation of the host brains revealed that the overall size of transplanted mesencephalic tissue was significantly increased in the GDNF-treated animals, and that the average size of transplanted tyrosine hydroxylase (TH)-positive neurons was also increased. Furthermore, we found that the innervation density of surrounding host striatal tissue was significantly increased in the GDNF-treated group, as compared with controls. Taken together, these results suggest that treatment of intrastriatal ventral mesencephalon grafts with GDNF can optimize the conditions for intracranial grafting and thus improve the chances for functional recovery following the intrastriatal grafting procedure.",
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