Reduction of GluR2 RNA editing, a molecular change that increases calcium influx through AMPA receptors, selective in the spinal ventral gray of patients with amyotrophic lateral sclerosis

Enhancement of calcium influx through the alpha-amino-3-hydroxy-5-methyl-4- isoxazole (AMPA)/kainate receptor is a plausible mechanism underlying selec tive neuronal death in amyotrophic lateral sclerosis (ALS). The calcium con ductance of the AMPA receptor is regulated by the GluR2 subunit that is edi ted at the glutamine/arginine residue site in the subunit assembly. We inve stigated the molecular changes of GluR2 mRNA in the spinal cord of ALS case s, those of cases with other neurological diseases, and those of normal cas es using reverse transcription-polymerase chain reaction combined with rest riction enzyme cleavage. We found that the editing efficiency was significa ntly lower only in the ventral gray of ALS cases (virtually 0% in 2 cases) than in any spinal region of the disease controls and normal controls. In a ddition, expression of GluR2 mRNA is lower in the ventral gray of the ALS c ases and disease controls than in that of the normal controls. The above mo lecular changes of GluR2 mRNA in the ventral gray of ALS cases may enhance calcium influx through AMPA receptors, thereby promoting neuronal vulnerabi lity. The decrement of GluR2 mRNA editing efficiency is unique to the ventr al gray of ALS cases and may be closely linked to the etiology of ALS.