Non-NMDA receptors in motor neuron disease (MND): a quantitative autoradiographic study in spinal cord and motor cortex using [3H]CNQX and [3H]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 [3H]CNQX and [3H]kainate. In the motor cortex of MND cases, an increased density of [3H]kainate binding sites was observed which was most marked in the deep layers. No significant differences were observed in [3H]CNQX binding in the motor cortex between MND and control cases. In the spinal cord significantly increased densities of both [3H]CNQX and [3]kainate binding sites were found in the substantia gelatinosa and the intermediate grey matter in the MND group. The changes in [3H]kainate binding were observed only in the amyotrophic lateral sclerosis (ALS) subgroup of MND, while the changes in [3H]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.
Shaw
P J
PJ
Department of Clinical Neurosciences, University of Newcastle upon Tyne, UK.
Chinnery
R M
RM
Ince
P G
PG
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000328:Adult; D000368:Aged; D001345:Autoradiography; D005260:Female; D006801:Humans; D007608:Kainic Acid; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism* / Q000473:pathology; D016472:Motor Neuron Disease / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000502:physiology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007608:Kainic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors