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Expression of an activated integrin promotes long-distance sensory axon regeneration in the spinal cord

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Andrews_2016_JoN_Expression_CCBY_FinalPublishedVersion.pdf (7.198Mb)
Date
06/07/2016
Author
Cheah, Menghon
Andrews, Melissa Renee
Chew, Daniel
Moloney, Elizabeth
Verhaagen, Joost
Fassler, Reinhard
Fawcett, James
Keywords
Adeno-associated virus
Alpha9 integrin
Axon regeneration
Dorsal root ganglion
Kindlin-1
Spinal cord
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Neuroscience(all)
NDAS
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Abstract
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.
Citation
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 . https://doi.org/10.1523/JNEUROSCI.0901-16.2016
Publication
The Journal of Neuroscience
Status
Peer reviewed
DOI
https://doi.org/10.1523/JNEUROSCI.0901-16.2016
ISSN
0270-6474
Type
Journal article
Rights
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.
Description
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.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/9117

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