title: Upregulation of EphA3 receptor after spinal cord injury.
abstract: Spinal cord injury (SCI) releases a cascade of events that leads to the onset of an inhibitory milieu for axonal regeneration. Some of these changes result from the presence of repulsive factors that may restrict axonal outgrowth after trauma. The Eph receptor tyrosine kinase (RTK) family has emerged as a key repellent cue known to be involved in neurite outgrowth, synapse formation, and axonal pathfinding during development. Given the nonpermissive environment for axonal regeneration after SCI, we questioned whether re-expression of one of these molecules occurs during regenerative failure. We examined the expression profile of EphA3 at the mRNA and protein levels after SCI, using the NYU contusion model. There is a differential distribution of this molecule in the adult spinal cord and EphA3 showed an increase in expression after several injury models like optic nerve and brain injury. Standardized semi-quantitative RT-PCR analysis demonstrated a time-dependent change in EphA3 mRNA levels, without alterations in beta-actin levels. The basal level of EphA3 mRNA in the adult spinal cord is low and its expression was induced 2 days after trauma (the earliest time point analyzed) and this upregulation persisted for 28 days post-injury (the latest time point examined). These results were corroborated at the protein level by immunohistochemical analysis and the cell phenotype identified by double labeling studies. In control animals, EphA3 immunoreactivity was observed in motor neurons of the ventral horn but not in lesioned animals. In addition, GFAP-positive cells were visualized in the ventral region of injured white matter. These results suggest that upregulation of EphA3 in reactive astrocytes may contribute to the repulsive environment for neurite outgrowth and may be involved in the pathophysiology generated after SCI.
authors.affiliation: Department of Clinical Laboratory Science, University of Puerto Rico Medical Science Campus, San Juan, Puerto Rico.
authors.forename: Margarita
authors.initials: M
authors.lastname: Irizarry-Ramírez
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Willson
authors.forename: Lillian
authors.initials: L
authors.lastname: Cruz-Orengo
authors.forename: Johnny
authors.initials: J
authors.lastname: Figueroa
authors.forename: Ixane
authors.initials: I
authors.lastname: Velázquez
authors.forename: Hope
authors.initials: H
authors.lastname: Jones
authors.forename: Roy D
authors.initials: RD
authors.lastname: Foster
authors.forename: Scott R
authors.initials: SR
authors.lastname: Whittemore
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Miranda
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D006131:Growth Inhibitors; D012333:RNA, Messenger; C110404:Epha3 protein, rat; D020794:Receptor Protein-Tyrosine Kinases