Expression of an activated integrin promotes long-distance sensory axon regeneration in the spinal cord
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After CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth of axons if they express a tenascin-binding integrin, particularly α9β1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a β1-binding integrin activator, kindlin-1. We examined the synergistic effect of α9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6–C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (25mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of α9 integrin or kindlin-1 alone promoted much less regeneration and recovery.
Cheah , M , Andrews , M R , Chew , D , Moloney , E , Verhaagen , J , Fassler , R & Fawcett , J 2016 , ' Expression of an activated integrin promotes long-distance sensory axon regeneration in the spinal cord ' The Journal of Neuroscience , vol 36 , no. 27 , pp. 7283-7297 . DOI: 10.1523/JNEUROSCI.0901-16.2016
The Journal of Neuroscience
Copyright © 2016 the Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
This work was supported by grants from the Christopher and Dana Reeve Foundation, the Medical Research Council, the European Research Council ECMneuro, and the Cambridge National Health and Medical Research Council Biomedical Research Centre.