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Inhibition of EphA7 up‐regulation after spinal cord injury reduces apoptosis and promotes locomotor recovery
Author(s) -
Figueroa Johnny D.,
Benton Richard L.,
Velazquez Ixane,
Torrado Aranza I.,
Ortiz Cristina M.,
Hernandez Carmen M.,
Diaz Juan J.,
Magnuson David S.,
Whittemore Scott R.,
Miranda Jorge D.
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21048
Subject(s) - erythropoietin producing hepatocellular (eph) receptor , ephrin , biology , spinal cord , spinal cord injury , neuroscience , receptor , microbiology and biotechnology , receptor tyrosine kinase , signal transduction , biochemistry
Functional impairment after spinal cord injury (SCI) is partially attributed to neuronal cell death, with further degeneration caused by the accompanying apoptosis of myelin‐forming oligodendrocytes. The Eph receptor protein tyrosine kinase family and its cognate ligands, the ephrins, have been identified to be involved in axonal outgrowth, synapse formation, and target recognition, mainly mediated by repulsive activity. Recent reports suggest that ephrin/Eph signaling might also play a role as a physiological trigger for apoptosis during embryonic development. Here, we investigated the expression profile of EphA7, after SCI, by using a combination of quantitative real‐time PCR (QRT‐PCR) and immunohistochemical techniques. QRT‐PCR analysis showed an increase in the expression of full‐length EphA7 at 7 days postinjury (DPI). Receptor immunoreactivity was shown mostly in astrocytes of the white matter at the injury epicenter. In control animals, EphA7 expression was observed predominantly in motor neurons of the ventral gray matter, although some immunoreactivity was seen in white matter. Furthermore, blocking the expression of EphA7 after SCI using antisense oligonucleotides resulted in significant acceleration of hindlimb locomotor recovery at 1 week. This was a transient effect; by 2 weeks postinjury, treated animals were not different from controls. Antisense treatment also produced a return of nerve conduction, with shorter latencies than in control treated animals after transcranial magnetic stimulation. We identified EphA7 receptors as putative regulators of apoptosis in the acute phase after SCI. These results suggest a functional role for EphA7 receptors in the early stages of SCI pathophysiology. © 2006 Wiley‐Liss, Inc.