Chapter 25 Transplantation of fetal dopamine neurons in primate brain reverses MPTP induced parkinsonism

Abstract

Parkinsonian signs were produced in the African Green monkeys by the administration of the toxin, 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). The transplantation of fetal neurons from the substantia nigra into two monkeys with severe symptoms of hypokinesia, postural and resting tremor, the episodes of movement freezing, and difficulty in initiating movements resulted in a reversal of these symptoms. The functional degree of recovery corresponded with the immunohistochemical observation of tyrosine hydroxylase (TH) positive neurons in the host caudate nucleus and putamen in these two animals. Dopamine metabolite levels in cerebrospinal fluid (CSF) were also elevated in these monkeys. A third monkey with parkinsonian signs received nigral tissue into a control site, the cingulate cortex. This animal failed to show recovery from the toxin-induced parkinsonism. Both early and late gestational tissue survived and showed growth of neurites, which suggested a wide developmental window in the primate brain. The combination of morphological evidence of survival and growth, the elevated neurochemical indices, and the reversal of behavioral motor impairment following the transplantation of fetal neurons into monkeys with parkinsonian signs may provide therapeutic insights into the treatment of Parkinson's disease.