Neurturin enhances the survival of intrastriatal fetal dopaminergic transplants.
We investigated here the effect of the novel glial cell line-derived neurotrophic factor (GDNF)-family member neurturin (NTN) on transplanted fetal dopamine (DA) neurons. Three groups of rats with complete unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal DA system received intrastriatal grafts of embryonic ventral mesencephalic tissue. Following transplantation animals received repeated injections of vehicle or NTN (0.3 microg or 3.0 microg) over three weeks posttransplantation. NTN-treated animals had significantly (1.8-fold) more tyrosine hydroxylase-immunoreactive (TH-IR) neurons. Graft volume, TH-IR cell volume and overall dopaminergic host reinnervation remained unchanged. Amphetamine-induced rotation was rapidly compensated in all grafted rats. We conclude that administration of NTN may be a powerful way to increase survival of transplanted fetal DA neurons.
Rosenblad
C
C
Department of Physiological Sciences, Wallenberg Neuroscience Center, University of Lund, Sweden.
Kirik
D
D
Björklund
A
A
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D017072:Neostriatum / Q000201:enzymology / Q000601:surgery*; D009412:Nerve Fibers / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism / Q000637:transplantation*; D051101:Neurturin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D009414:Nerve Growth Factors; D051101:Neurturin; C495057:Nrtn protein, rat; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine