METABOLIC-ACTIVITY OF THE BASAL GANGLIA IN PARKINSONIAN SYNDROMES IN HUMAN AND NONHUMAN-PRIMATES - A CYTOCHROME-OXIDASE HISTOCHEMISTRY STUDY

In order to examine the consequences of nigrostriatal denervation on m etabolic and functional activity of the basal ganglia, we analysed the distribution of cytochrome oxidase, a metabolic marker for neuronal f unctional activity, throughout the different basal ganglia structures in parkinsonian syndromes. The study was performed using enzyme histoc hemistry and densitometric measurements in patients with Parkinson's d isease and in monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3 ,6-tetrahydropyrydine (MPTP) intoxication. In MPTP-intoxicated monkeys compared to control animals, enzyme activity was significantly increa sed in the subthalamic nucleus and in the output nuclei of the basal g anglia, e.g. the internal segment of the globus pallidus and the subst antia nigra pars reticulata, but remained unchanged in the external se gment of the globus pallidus and the striatum. L-DOPA treatment revers ed the increased enzyme activity in all of the affected structures stu died. In contrast, in parkinsonian patients, who had all been chronica lly treated with L-DOPA, no changes in enzyme activity were detected c ompared to control subjects. The results in MPTP-intoxicated monkeys a re in agreement with the accepted model of basal ganglia organization, in which the output nuclei of the basal ganglia are considered to be overactive after nigrostriatal denervation, partly due to increased ac tivity of excitatory afferents from the subthalamic nucleus. Since the increased enzyme activity in MPTP-intoxicated monkeys was reversed by L-DOPA therapy, the unchanged cytochrome oxidase activity observed in parkinsonian patients might result from L-DOPA treatment, combined wi th the chronicity of nigrostriatal denervation.