Distribution of the N-methyl- d-aspartate glutamate receptor subunit NR2A in control and amyotrophic lateral sclerosis spinal cord

Abstract

The distribution of the different glutamate receptor subunits in human spinal cord has yet to be fully elucidated. The aim of this study was to examine the distribution of the N-methyl- d-aspartate (NMDA) glutamate receptor modulatory subunit NR2A, in control human spinal cord and to examine in parallel the expression of the mRNA in amyotrophic lateral sclerosis (ALS). The aetiology of ALS is poorly understood, although abnormalities in glutamate and glycine transport have been reported as well as alterations in NMDA receptors including the NRl subunit; suggesting a role for glutamate in the disease process. We have used the technique of in situ hybridisation to localise this receptor subunit to the laminae of human spinal cord and have found that it shows a widespread distribution similar to that previously reported for the universal NMDA receptor subunit NR1. Quantitation of mRNA expression in control and ALS cases showed a significant widespread loss of NR2A from both dorsal and ventral horns with losses of 55% and 78%, respectively. in ALS as compared to control, These results were substantiated by analysis of spinal cord homogenates, which showed a significant total decrease of 50% in ALS spinal cord as compared to control.