CONSEQUENCES OF NIGROSTRIATAL DENERVATION ON THE FUNCTIONING OF THE BASAL GANGLIA IN HUMAN AND NONHUMAN-PRIMATES - AN IN-SITU HYBRIDIZATIONSTUDY OF CYTOCHROME-OXIDASE SUBUNIT-I MESSENGER-RNA

To examine the consequences of nigrostriatal denervation and chronic l evodopa (L-DOPA) treatment on functional activity of the basal ganglia , we analyzed, using in situ hybridization, the cellular expression of the mRNA encoding for cytochrome oxidase subunit I (COI mRNA), a mole cular marker for functional neuronal activity, in the basal ganglia. T his analysis was performed in monkeys rendered parkinsonian by 1-methy l-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication, some of whi ch had been receiving L-DOPA, and in patients with Parkinson's disease (PD). In MPTP-intoxicated monkeys compared with control animals, COI mRNA expression was increased in the subthalamic nucleus (STN) and in the output nuclei of the basal ganglia, i.e., the internal segment of the globus pallidus and the substantia nigra pars reticulata. This inc rease was partially reversed by L-DOPA treatment. COI mRNA expression remained unchanged in the external segment of the globus pallidus (GPe ). In PD patients, all of whom had been treated chronically by L-DOPA, COI mRNA expression in the analyzed basal ganglia structures was simi lar to that in control subjects. These results are in agreement with t he accepted model of basal ganglia organization, to the extent that th e output nuclei of the basal ganglia are considered to be overactive a fter nigrostriatal denervation, partly because of increased activity o f excitatory afferents from the STN. Yet, our results would also seem to contradict this model, because the overactivity of the STN does not seem to be attributable to a hypoactivation of the GPe.