Temporal changes in the neurotrophic environment of the denervated striatum as determined by the survival and outgrowth of grafted fetal dopamine neurons.
There is growing evidence that the neurotrophic environment of the denervated striatum may change with time following a lesion of the nigrostriatal pathway in young adult rats. To test this hypothesis, we implanted fetal dopamine grafts into the striatum at several different time points relative to the nigrostriatal pathway lesion and allowed the grafts to integrate with the host for a period of 1 month; subsequently, we observed the function and morphology of the dopamine grafts. Fetal grafts were implanted at the following time points relative to the lesion: 1 week before (-1 Week), at the same time (Week 0), 1 week after (1 Week), 4 weeks after (4 Weeks), or 12 weeks after (12 Weeks). Amphetamine-induced rotational behavior was assessed 4 weeks after grafting for all groups. Rotational scores indicate that grafts for the 1 Week group showed the greatest reversal of amphetamine-induced rotational behavior that was also significantly greater than the scores for the -1 Week group. Morphological analysis revealed that grafts in the Week 0, 1 Week and 4 Weeks groups showed a significantly larger area of tyrosine hydroxylase-positive (TH+) fiber outgrowth than in the -1 Week group, while fiber outgrowth for the 12 Weeks group was significantly lower than for the 1 Week group. Cell count analysis for TH+ neurons within the graft indicate a significantly greater number of TH+ neurons in grafts for the 1 Week group than in grafts for the -1 Week. The results of this study suggest that neurotoxic lesions may induce a compensatory increase in neurotrophic activity within the denervated striatum of young rats that is conducive to the survival and outgrowth of fetal dopamine grafts. These data also correlate well with reports that the expression of several specific dopaminergic neurotrophic factors within the striatum increase following a neurotoxic lesion of the nigrostriatal pathway in young adult rats.
Yurek
David M
DM
Department of Surgery/Neurosurgery, University of Kentucky College of Medicine, Health Sciences Research Building, Lexington 40536-0305, USA. dyure00@uky.edu
Fletcher-Turner
Anita
A
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016380:Brain Tissue Transplantation; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism; D016332:Fetal Tissue Transplantation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006085:Graft Survival; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D023421:Models, Animal; D009412:Nerve Fibers / Q000502:physiology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine