3H] d-aspartate binding sites in the normal human spinal cord and changes in motor neuron disease: a quantitative autoradiographic study

Abstract

The distribution and density of glutamate transporter sites was determined in human cervical and lumbar spinal cord, by quantitative autoradiography using [ 3H] d-aspartate. In the normal human spinal cord ( n = 8) there was specific binding of [ 3H] d-aspartate throughout the spinal grey matter, with the highest levels observed in the substantia gelatinosa and central grey matter. In the ventral horns, particularly at the L5 level, focal hot spots of binding were observed in a distribution corresponding to that of lower motor neuron somata. Comparison of motor neuron disease (MND) cases ( n = 12) with normal controls showed a reduction in the density of [ 3H] d-aspartate binding in the intermediate grey matter and the substantia gelatinosa of the lumbar cord. These changes were more marked in the amyotrophic lateral sclerosis (ALS) compared to the progressive muscular atrophy (PMA) subgroup, and may be due to loss of glutamatergic terminals of the corticospinal tract. The changes observed in the cervical cord were milder and did not reach statistical significance. No differences were found between [ 3H] d-aspartate binding in the spinal cords of the normal controls and a neurological disease control group ( n = 6), suggesting that the changes observed in MND are disease specific. These findings provide further evidence in support of a disturbance of glutamatergic neurotransmission in MND.