A post mortem study on neurochemical markers of dopaminergic, GABA-ergic and glutamatergic neurons in basal ganglia thalamocortical circuits in Parkinson syndrome

Functional models of the circuitry of the basal ganglia have recently been proposed to account for the vast spectrum of motor disorders associated with the loss of anatomical or neurochemical integrity within the basal ganglia. On the basis of these hypothetical models, hypokinetic disorders such as Parkinson's disease, are thought to be associated with excessive tonic and phasic inhibition of the output from the basal ganglia to the thalamus. In the present study we have attempted to determine the validity of the proposed model by measuring neurochemical markers of inhibitory and excitatory neurotransmission in post mortem human brain tissue, We have determined the concentrations of the excitatory neurotransmitters aspartate/glutamate and of the inhibitory neurotransmitter GABA in 18 relevant regions of the thalamocortical circuits of the basal ganglia of patients who had manifested Parkinsonian symptoms, and compared them with controls of individuals who had died without any history of neurological or psychiatric disorders and had no neuropathological abnormalities. Additionally, the receptor subtype for the excitatory amino acid N-methyl-D-aspartate (NMDA) was studied in the same brain tissue in which neurotransmitter concentrations had been analysed as neurochemical markers of post-synaptic excitatory neurotransmission. In patients who had manifested Parkinsonian symptoms, glutamate and aspartate levels were found to be unchanged in all examined brain regions. In contrast, the binding of [H-3]MK-801, which identifies the NMDA receptor, was reduced in the head (-42%) and body (-38%) of the caudate nucleus. In Parkinsonian patients, GABA levels were diminished by 36% in the centromedial thalamus, compared to control values. These results do not confirm the changes in neurotransmitter concentrations predicted according to the model, although we cannot rule out that the predicted changes might have been observed if the Parkinsonian group had been further subdivided into groups diagnosed on the basis of the patients' clinical picture (akinetic-rigid, tremor-dominant, equivalent type) and compared with the control group.