Glial cell line-derived neurotrophic factor improves survival of dopaminergic neurons in transplants of fetal ventral mesencephalic tissue.
This study was designed to determine whether or not an exogenous source of glial cell line-derived neurotrophic factor (GDNF) could be delivered continuously into the denervated/transplanted striatum and stimulate the survival, growth, and function of fetal ventral mesencephalic tissue transplants. Adult male rats with unilateral 6-hydroxydopamine lesions received transplants of fetal ventral mesencephalic tissue into the denervated striatum. Immediately thereafter, osmotic pumps [Alzet 2002, 0.5 microliter/h] were attached to intracerebral cannula and either a citrate buffer alone [control] or r-methuGDNF [dissolved in sodium citrate buffer to a concentration of 0.45 microgram/microliter] was infused into a site approximately 1.0 mm lateral to the transplant for a 2-week period; one group of lesioned animals did not receive transplants but was infused with GDNF. The effect of GDNF on tyrosine hydroxylase-positive (TH+) fiber outgrowth from transplants was variable, and image analysis revealed no significant difference between the GDNF and citrate groups. In contrast, the mean number of TH+ cells bodies in transplants infused with GDNF [2,037 +/- 149, n = 8] vs citrate [663 +/- 160, n = 8] was statistically significant (P < 0.001); cell counts were made in every third brain section [35 micrometer]. Similarly, transplants infused with GDNF showed an over-compensatory effect to amphetamine-induced rotational behavior that was significantly lower than that observed in transplanted animals receiving citrate buffer infusions. Infusions of GDNF into the denervated striatum alone had no significant effect on amphetamine-induced rotational behavior or on TH fiber morphology in the lesioned striatum. Thus, a continuous infusion of GDNF can improve the survivability of dopaminergic neurons in transplants of fetal ventral mesencephalic tissue.
Department of Surgery/Neurosurgery, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
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D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D016380:Brain Tissue Transplantation / Q000473:pathology / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D016332:Fetal Tissue Transplantation / Q000473:pathology / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D007263:Infusions, Parenteral; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000637:transplantation*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012399:Rotation; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine