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 subunits: 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 spinal trauma. We tested the hypothesis that SCI alters expression of AMPA receptors using a standardized thoracic weight-drop model of rat contusive spinal cord injury. AMPA receptor subunit expression was measured at 24 hr and at 1 month after SCI with quantitative Western blot analysis and in situ hybridization. GluR2 protein levels were preferentially reduced near the injury 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 spared ventral motor neurons adjacent to the injury site and distal to it, with other AMPA subunit mRNAs maintained at control levels. In contrast, only GluR1 mRNA was decreased in the sympathetic preganglionic neurons of the intermediolateral horn. These results suggest population-specific and long-lasting changes in neuronal AMPA receptor composition, which may alter response to glutamate after SCI. These alterations may contribute not only to acute neuropathological consequences of injury, but they may also be partially responsible for the altered functional state of preserved tissue seen chronically after SCI.
Grossman
S D
SD
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Wolfe
B B
BB
Yasuda
R P
RP
Wrathall
J R
JR
D000818:Animals; D016375:Antisense Elements (Genetics); D001345:Autoradiography; D001483:Base Sequence; D003288:Contusions; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009043:Motor Activity; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000235:genetics*; D012018:Reflex; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014158:Transcription, Genetic
D016375:Antisense Elements (Genetics); D012333:RNA, Messenger; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2