Alterations in AMPA receptor subunit expression after experimental spinal cord contusion injury

The AMPA-preferring subtype of ionotropic glutamate receptors (GluRs) is a hetero-oligomeric ion channel assembled from various combinations of four s ubunits: GluR1, GluR2, GluR3, and GluR4. Antagonists of these receptors can mitigate the effects of experimental spinal cord injury (SCI), indicating that these receptors play a significant role in pathophysiology after spina l trauma. We tested the hypothesis that SCI alters expression of AMPA recep tors using a standardized thoracic weight-drop model of rat contusive spina l cord injury. AMPA receptor subunit expression was measured at 24 hr and a t 1 month after SCI with quantitative Western blot analysis and in situ hyb ridization. GluR2 protein levels were preferentially reduced near the injur y site 24 hr after SCI. This reduction persisted at 1 month. At a cellular level, a significant decrease in both GluR2 and GluR4 mRNA was found in spa red ventral motor neurons adjacent to the injury site and distal to it, wit h other AMPA subunit mRNAs maintained at control levels. In contrast, only GluR1 mRNA was decreased in the sympathetic preganglionic neurons of the in termediolateral horn. These results suggest population-specific and long-la sting changes in neuronal AMPA receptor composition, which may alter respon se to glutamate after SCI. These alterations may contribute not only to acu te neuropathological consequences of injury, but they may also be partially responsible for the altered functional state of preserved tissue seen chro nically after SCI.