Upregulation of EphA3 receptor after spinal cord injury

Margarita Irizarry-Ramírez, Christopher A. Willson, Lillian Cruz-Orengo, Johnny Figueroa, Ixane Velázquez, Hope Jones, Roy D. Foster, Scott R. Whittemore, Jorge D. Miranda

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 β-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.

Original languageEnglish (US)
Pages (from-to)929-935
Number of pages7
JournalJournal of Neurotrauma
Volume22
Issue number8
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

EphA3 Receptor
Spinal Cord Injuries
Up-Regulation
Wounds and Injuries
Messenger RNA
Regeneration
Spinal Cord
Eph Family Receptors
Optic Nerve Injuries
Contusions
Motor Neurons
Horns
Astrocytes
Synapses
Brain Injuries
Cues
Actins
Proteins
Phenotype
Polymerase Chain Reaction

Keywords

  • Astrocytes
  • Ephrins
  • Immunohistochemistry
  • Regeneration
  • RT-PCR
  • Trauma

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Irizarry-Ramírez, M., Willson, C. A., Cruz-Orengo, L., Figueroa, J., Velázquez, I., Jones, H., ... Miranda, J. D. (2005). Upregulation of EphA3 receptor after spinal cord injury. Journal of Neurotrauma, 22(8), 929-935. https://doi.org/10.1089/neu.2005.22.929

Upregulation of EphA3 receptor after spinal cord injury. / Irizarry-Ramírez, Margarita; Willson, Christopher A.; Cruz-Orengo, Lillian; Figueroa, Johnny; Velázquez, Ixane; Jones, Hope; Foster, Roy D.; Whittemore, Scott R.; Miranda, Jorge D.

In: Journal of Neurotrauma, Vol. 22, No. 8, 01.08.2005, p. 929-935.

Research output: Contribution to journalArticle

Irizarry-Ramírez, M, Willson, CA, Cruz-Orengo, L, Figueroa, J, Velázquez, I, Jones, H, Foster, RD, Whittemore, SR & Miranda, JD 2005, 'Upregulation of EphA3 receptor after spinal cord injury', Journal of Neurotrauma, vol. 22, no. 8, pp. 929-935. https://doi.org/10.1089/neu.2005.22.929
Irizarry-Ramírez M, Willson CA, Cruz-Orengo L, Figueroa J, Velázquez I, Jones H et al. Upregulation of EphA3 receptor after spinal cord injury. Journal of Neurotrauma. 2005 Aug 1;22(8):929-935. https://doi.org/10.1089/neu.2005.22.929
Irizarry-Ramírez, Margarita ; Willson, Christopher A. ; Cruz-Orengo, Lillian ; Figueroa, Johnny ; Velázquez, Ixane ; Jones, Hope ; Foster, Roy D. ; Whittemore, Scott R. ; Miranda, Jorge D. / Upregulation of EphA3 receptor after spinal cord injury. In: Journal of Neurotrauma. 2005 ; Vol. 22, No. 8. pp. 929-935.
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