GLUTAMATE DECARBOXYLASE-67 MESSENGER-RNA EXPRESSION IN NORMAL HUMAN BASAL GANGLIA AND IN PARKINSONS-DISEASE

Expression of glutamate decarboxylase-67 messenger RNA was examined in the basal ganglia of normal controls and of cases of Parkinson's dise ase using in situ hybridization histochemistry in human post mortem ma terial. In controls glutamate decarboxylase-67 messenger RNA expressio n was detected in all large neurons in both segments of the globus pal lidus and in three neuronal subpopulations in the striatum as well as in substantia nigra reticulata neurons and in a small sub-population o f subthalamic neurons. In Parkinson's disease, there was a statistical ly significant decrease of 50.7% in glutamate decarboxylase-67 messeng er RNA expression per neuron in the lateral segment of the globus pall idus (controls: mean 72.8 mu m(2) +/- S.E.M. 8.7 of silver grain/neuro n, n=12; Parkinson's disease: mean 35.9 mu m(2) +/- S.E.M. 9.7 of silv er grain/neuron, n=9, P=0.01, Student's t-test). In the medial segment of the globus pallidus, there was a small, but non-significant decrea se of glutamate decarboxylase-67 messenger RNA expression in Parkinson 's disease (controls: mean 100.6 mu m(2) +/- S.E.M. 7.2 of silver grai n/neuron, n=11; Parkinson's disease: mean 84.8 mu m(2) +/- S.E.M. 13.0 of silver grain/neuron, n=7, P=0.1, Student's t-test). No significant differences in glutamate decarboxylase-67 messenger RNA were detected in striatal neuronal sub-populations between Parkinson's disease case s and controls. These results are the first direct evidence in humans that there is increased inhibitory drive to the lateral segment of the globus pallidus in Parkinson's disease, as suggested by data from ani mal models. We therefore provide theoretical support for current exper imental neurosurgical approaches to Parkinson's disease. Copyright (C) 1996 IBRO.