PREPROENKEPHALIN AND PREPROTACHYKININ MESSENGER-RNA EXPRESSION IN NORMAL HUMAN BASAL GANGLIA AND IN PARKINSONS-DISEASE

Striatal expression of preproenkephalin and preprotachykinin messenger RNA was studied in normal controls and in patients with Parkinson's d isease using in situ hybridization histochemistry. In controls, prepro enkephalin messenger RNA was expressed in a population of medium-sized neurons of mean cross-sectional area 165 mu m(2), accounting for 66% of striatal medium-sized neurons, whereas preprotachykinin messenger R NA was expressed in a population of medium-sized neurons of mean cross -sectional area 204 mu m(2) (23% larger than those expressing enkephal in, P < 0.05), accounting for 58% of medium-sized striatal neurons. Mu ch lower levels of both preproenkephalin messenger RNA and preprotachy kinin messenger RNA were expressed by large neurons in the globus pall idus and substantia nigra reticulata. In addition, preproenkephalin me ssenger RNA was expressed at low levels by neurons in the subthalamic nucleus. In Parkinson's disease cases, there was a statistically signi ficant increase in preproenkephalin messenger RNA expression in the bo dy of the caudate (109% increase, P < 0.05) and in the intermediolater al putamen (55% increase, P < 0.05) due to an increase in the level of gene expression per neuron rather than an increase in the number of n eurons expressing preproenkephalin messenger RNA. Similar increases we re observed in other putaminal subregions and in the putamen as a whol e, but these did not reach statistical significance. No change in prep rotachykinin messenger RNA expression was detected. These findings dem onstrate selective up-regulation of a striatal neuropeptide system in Parkinson's disease compatible with increased activity of the ''indire ct'' striatopallidal pathway, which is thought to play a crucial role in the pathophysiology of akinesia and rigidity in this condition.