Molecular Changes of AMPA receptor subunits in ALS spinal cord

To investigate the role of AMPA receptor-mediated neuronal death in amyotrophic lateral sclerosis (ALS), we investigated the molecular change of GluR2 mRNA relevant to Ca permeability of AMPA receptors in the spinal cord of ALS cases compared with the spinal cord of cases with other neurological diseases and that of normal cases using reverse transcription-polymerase chain reaction (RT-PCR) combined with restriction enzyme cleavage. We found that expression of GluR2 mRNA is lower in the ventral gray of the ALS cases and disease controls than that in the normal controls. In addition, the editing efficiency was significantly lower only in the ventral gray of ALS cases than in any spinal region of the disease and normal controls. The above molecular changes of GluR2 mRNA may increase calcium influx through AMPA receptors, thereby promoting neuronal vulnerability. The decrement of GluR2 mRNA editing has not been demonstrated in any experimental or disease condition and is specific to the ALS ventral gray, suggesting that it is closely linked to the etiology of ALS.