Accumulation of the inhibitory receptor EphA4 may prevent regeneration of corticospinal tract axons following lesion.
Abstract We have examined the expression of Eph receptors and their ephrin ligands in adult rat spinal cord before and after lesion. Neurons in adult motor cortex express EphA4 mRNA, but the protein is undetectable in uninjured corticospinal tract. In contrast, after dorsal column hemisection EphA4 protein accumulates in proximal axon stumps. One of the ligands for EphA4, ephrinB2, is normally present in the grey matter flanking the corticospinal tract but after injury is markedly up-regulated in astrocytes in the glial scar. The result is that, after a lesion, corticospinal tract axons bear high levels of EphA4 and are surrounded to front and sides by a continuous basket of cognate inhibitory ephrin ligand. We suggest that a combination of EphA4 accumulation in the injured axons and up-regulation of ephrinB2 in the surrounding astrocytes leads to retraction of corticospinal axons and inhibition of their regeneration in the weeks after a spinal lesion.
Fabes
Jez
J
Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
Anderson
Patrick
P
Yáñez-Muñoz
Rafael J
RJ
Thrasher
Adrian
A
Brennan
Caroline
C
Bolsover
Stephen
S
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D036388:Ephrin-B2 / Q000096:biosynthesis; D036389:Ephrin-B3 / Q000096:biosynthesis; D005260:Female; D008024:Ligands; D009044:Motor Cortex / Q000378:metabolism / Q000648:ultrastructure*; D009416:Nerve Regeneration; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D036081:Receptors, Eph Family / Q000096:biosynthesis*; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
D036388:Ephrin-B2; D036389:Ephrin-B3; D008024:Ligands; D036081:Receptors, Eph Family