Regional metabolic changes in the pedunculopontine nucleus of unilateral 6-hydroxydopamine Parkinson's model rats

Abstract

The pedunculopontine nucleus (PPN) located in the mesopontine tegmentum is innervated by descending projections from nuclei in the basal ganglia. The present study was performed to determine whether nigrostriatal dopaminergic neuron degeneration is associated with changes in PPN metabolic activity. Unilateral nigrostriatal lesioning was performed by injecting 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta in 10 rats. Six of these animals exhibited apomorphine-induced rotations contralateral to the lesion and were included in the experimental group for determination of regional cerebral metabolic rate for glucose (rCMR glucose) along with five sham-lesioned and five normal controls. All studies were performed 13–15 days after lesioning using [14] C -2-deoxyglucose autoradiography. Significant hemispheric differences in metabolic activity were observed only in the 6-OHDA lesioned animals. Increased rCMR glucose was found in the globus pallidus (+63%) ipsilateral to the lesion as compared to the contralateral hemisphere, and reduced rCMR glucose in the primary motor, sensory, and auditory cortex (−7%, −12% and −7%, respectively), and in the subthalamic nucleus (−6%). Metabolic activity within the PPN ipsilateral to the lesion was significantly greater than the contralateral hemisphere ( P<0.05; lesion 57±8, nonlesion 52±5), and significantly greater than the sham-lesioned side of the sham rat ( P<0.05; sham lesion 47±5). No hemispheric differences were observed in the lateral dorsal tegmental nucleus. These observations offer further support for a role of the PPN in Parkinson's and for the utility of the rodent unilateral 6-OHDA model in defining the pathophysiologic significance of the mesopontine tegmental striatal–motor interfaces in basal ganglia disease.