Upregulation of EphA receptor expression in the injured adult rat spinal cord.
After spinal cord injury (SCI), the inability of supraspinal neurons to regenerate or reform functional connections is likely due to proteins in the surrounding microenvironment restricting regeneration. EphAs are a family of receptor tyrosine kinases that are involved in axonal guidance during development. These receptors and their ligands, the Ephrins, act via repulsive mechanisms to guide growing axons towards their appropriate targets and allow for the correct developmental connections to be made. In the present study, we investigated whether EphA receptor expression changed after a thoracic contusion SCI. Our results indicate that several EphA molecules are upregulated after SCI. Using semiquantitative RT-PCR to investigate mRNA expression after SCI, we found that EphA3, A4, and A7 mRNAs were upregulated. EphA3, A4, A6, and A8 receptor immunoreactivity increased in the ventrolateral white matter (VWM) at the injury epicenter. EphA7 had the highest level of immunoreactivity in both control and injured rat spinal cord. EphA receptor expression in the white matter originated from glial cells as coexpression in both astrocytes and oligodendrocytes was observed. In contrast, gray matter expression was localized to neurons of the ventral gray matter (motor neurons) and dorsal horn. After SCI, specific EphA receptor subtypes are upregulated and these increases may create an environment that is unfavorable for neurite outgrowth and functional regeneration.
Willson
Christopher A
CA
Kentucky Spinal Cord Injury Research Center, and Department of Neurological Surgery, University of Louisville School of Medicine, 40202, USA.
Irizarry-Ramírez
Margarita
M
Gaskins
Hope E
HE
Cruz-Orengo
Lillian
L
Figueroa
Johnny D
JD
Whittemore
Scott R
SR
Miranda
Jorge D
JD
D000818:Animals; D036342:Ephrins / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism*; D015854:Up-Regulation
D036342:Ephrins; D020033:Protein Isoforms; D012333:RNA, Messenger; D036081:Receptors, Eph Family