Rapid changes in expression of glutamate transporters after spinal cord injury.
Glutamate is a major excitatory neurotransmitter in the mammalian CNS. After its release, specific transporter proteins rapidly remove extracellular glutamate from the synaptic cleft. The clearance of excess extracellular glutamate prevents accumulation under normal conditions; however, CNS injury elevates extracellular glutamate concentrations to neurotoxic levels. The purpose of this study was to examine changes in expression and in spatial localization of glial glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2) and the neuronal glutamate transporter EAAC1 (EAAT3) after spinal cord contusion injury (SCI). The levels of all three transporters significantly increased at the epicenter of injury (T10) and in segments rostral and caudal to the epicenter as determined by Western blot analysis. Quantitative immunohistochemistry demonstrated an increase in GLAST staining in laminae I-V and lamina X both rostral and caudal to the epicenter of injury. Staining for GLT-1 increased significantly in lamina I rostral to the injury site and in the entire gray matter caudal to the injury site. A significant increase in EAAC1 staining was observed in laminae I-IV rostral to the epicenter of injury and throughout the gray matter caudal to the injury site. The results suggest that upregulation of these high affinity transporters occurs rapidly and is important in regulating glutamate homeostasis after SCI.
Vera-Portocarrero
Louis P
LP
Department of Anatomy and Neurosciences, University of Texas Medical Branch at Galveston, Medical Research Bldg., Rm. 10.138, 301 University Blvd., Galveston, TX 77555-1043, USA.
Mills
Charles D
CD
Ye
Zaiming
Z
Fullwood
Steven D
SD
McAdoo
David J
DJ
Hulsebosch
Claire E
CE
Westlund
Karin N
KN
D027322:Amino Acid Transport System X-AG / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2 / Q000032:analysis / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism*; D027981:Symporters
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D027981:Symporters; D018698:Glutamic Acid