Changes in NMDA receptor subunit expression in response to contusive spinal cord injury

Differential assembly of N-methyl-D-aspartate (NMDA) receptor subunits dete rmines their functional characteristics. Using in situ hybridization, we fo und a selective increase of the subunits NR1 and NR2A mRNA at 24 h in ventr al motor neurons (VMN) caudal to a standardized spinal cord contusion injur y (SCI). Other neuronal cell populations and VMN rostral to the injury site appeared unaffected. Significant up-regulation of NR2A mRNA also was seen 1 month after SCI in thoracic and lumbar VMN. The selective effects on VMN caudal to the injury site suggest that the loss of descending innervation l eads to increased NMDA receptor subunit expression in these cells after SCI , which may alter their responses to glutamate. in contrast, protein levels determined by western blot analysis show decreased levels of NR2A 1 month after SCI in whole thoracic segments of spinal cord that included the injur y sites. No effects of injury were seen on subunit levels in cervical or lu mbar segments. Taken together with our previous study showing alpha-amino-3 -hydroxy-5-methyl-4-isoxazole propionate receptor subunit down-regulation a fter injury, our data suggest that glutamate receptor composition is signif icantly altered after SCI. These changes need to be taken into account to p roperly understand the function of, and potential pharmacotherapy for, the chronically injured spinal cord.