Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys

摘要: Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum MPTP-exposed monkeys and humans in patients with idiopathic Parkinson's disease. While there is good evidence for survival grafted tyrosine hydroxylase (TH)-positive cells animal studies, it not known whether they produce neuronal effects that account behavioral improvement after or spontaneous graft-induced changes host are at least partly responsible. Are synaptic connections dopamine release necessary, would "toenails talcum powder" do job equally well? We have addressed these questions by studying several types implantation surgeries, including sham surgery, cerebellar tissue, TH-positive various gestational ages striatum. Adult male African green received systemic MPTP administration (cumulative doses 2.0-2.5 mg/kg) prior stereotaxic surgical manipulations. Subjects were matched quantitative deficits surgery. examined assessments made "blinded" observers who scored individual elicited behaviors. Observers trained tested repeatedly inter-rater reliability. A "parkinsonian summary score" derived determined using a principal component factor analysis large sample data from MPTP-treated normal same species was used assess behavior. Postmortem brain prepared biochemical concentrations TH immunohistochemical studies. The most dramatic seen "early" ( 14 cm crown rump length) substantia nigra-grafted monkeys. These which did surviving dopamine-producing grafts probably represent recovery capacity during this time interval since un-operated subjects showed similar changes. More variable nigra putamen. consistent correlate all experimental groups elevation near compared distant striatal location believed depletion without grafts. establish precise mechanism action, point hierarchy factors provide increasingly larger restorative effects, sprouting neurons increased production neurons. Sham surgery appears be significantly less effective than early survives releases dopamine.