Alterations in spinal cord excitatory amino acid receptors in amyotrophic lateral sclerosis patients

Abstract

Excitatory amino acids (EAA) have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We have analyzed the distribution of the N-methyl- d-aspartate (NMDA) 1-(1-(2-thienyl)-cyclohexyl) piperidine (TCP), kainate and α-amino-3-hydroxy-5-methyl-4 isoxazole proprionic acid (AMPA) quisqualate subtypes of EAA receptors using quantitative receptor autoradiography in the cervical and thoracic spinal cords of patients who have died with ALS, and of controls. We observed that in control spinal cords [ 3H]TCP/NMDA binding sites were located both in the ventral and dorsal horns with the highest densities being situated in lamina II. [ 3H]AMPA and [ 3H]kainate binding sites were present almost exclusively in the substantia gelatinosa of the dorsal horn. In ALS, the distribution of these 3 types of receptors was unchanged, but [ 3H]TCP/NMDA binding was decreased both in the dorsal and ventral horns. [ 3H]kainate binding was possibly decreased in substantia gelatinosa, of ALS cords. However, the limited sample size available for [ 3H]kainate binding did not permit statistical analysis. [ 3H]AMPA binding sites were unaltered in ALS. These results indicate that there is a preferential reduction in NMDA receptors in ALS. We suggest that should an excitotoxic mechanism be involved in the pathogenesis of ALS, then NMDA receptors may be the target of this effect.