NON-NMDA RECEPTORS IN MOTOR-NEURON DISEASE (MND) - A QUANTITATIVE AUTORADIOGRAPHIC STUDY IN SPINAL-CORD AND MOTOR CORTEX USING [H-3] CNQX AND [H-3] KAINATE

The distribution and density of non-NMDA receptors in spinal cord and motor cortex was compared in 10 cases of motor neuron disease (MND) and 8 neurologically normal controls by quantitative autoradiography using [H-3]CNQX and [H-3]kainate. In the motor cortex of MND cases, an increased density of [H-3]kainate binding sites was observed which was most marked in the deep layers. No significant differences were observed in [H-3]CNQX binding in the motor cortex between MND and control cases. In the spinal cord significantly increased densities of both [H-3]CNQX and [(3)]kainate binding sites were found in the substantia gelatinosa and the intermediate grey matter in the MND group. The changes in [H-3]kainate binding were observed only in the amyotrophic lateral sclerosis (ALS) subgroup of MND, while the changes in [H-3]CNQX binding in the spinal cord were more marked in ALS compared to progressive muscular atrophy (PMA) cases. These findings provide evidence in support of a disturbance of glutamatergic neurotransmission in MND and suggest that there may be an increased excitatory drive to motor neurons via non-NMDA receptors. It is unclear at present whether the changes observed represent a compensatory response to loss of motor neurons in MND or a pathophysiological phenomenon contributing to motor neuron degeneration. Modulation of non-NMDA receptor activity may represent a possible target for therapeutic intervention in this disease.