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

Expression of an activated integrin promotes long-distance sensory axon regeneration in the spinal cord
Expression of an activated integrin promotes long-distance sensory axon regeneration in the spinal cord
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 ?9?1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a ?1-binding integrin activator, kindlin-1. We examined the synergistic effect of ?9 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 (>25 mm 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 ?9 integrin or kindlin-1 alone promoted much less regeneration and recovery
7283-7297
Cheah, M.
b9fe8318-32a8-4135-ba1b-d5e07bbbf1e8
Andrews, Melissa
ae987a2f-878e-4ae3-a7a3-a7170712096c
Chew, D.J.
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Moloney, E.B.
1f164bfb-3097-4712-ae6b-5cc91e232e38
Verhaagen, J.
bddf3b8c-5441-4517-87aa-c53e14f7ccf2
Fassler, R.
47ba8a1c-d108-4de4-86e4-350d0576b908
Fawcett, J.W.
9fda4f52-4374-44cd-9ebd-b09558caa694
Cheah, M.
b9fe8318-32a8-4135-ba1b-d5e07bbbf1e8
Andrews, Melissa
ae987a2f-878e-4ae3-a7a3-a7170712096c
Chew, D.J.
e6bfac49-9fe6-44c5-9dca-0469f7e97d7a
Moloney, E.B.
1f164bfb-3097-4712-ae6b-5cc91e232e38
Verhaagen, J.
bddf3b8c-5441-4517-87aa-c53e14f7ccf2
Fassler, R.
47ba8a1c-d108-4de4-86e4-350d0576b908
Fawcett, J.W.
9fda4f52-4374-44cd-9ebd-b09558caa694

Cheah, M., Andrews, Melissa, Chew, D.J., Moloney, E.B., Verhaagen, J., Fassler, R. and Fawcett, J.W. (2016) Expression of an activated integrin promotes long-distance sensory axon regeneration in the spinal cord. Journal of Neuroscience, 36 (27), 7283-7297. (doi:10.1523/JNEUROSCI.0901-16.2016). (PMID:27383601)

Record type: Article

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 ?9?1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a ?1-binding integrin activator, kindlin-1. We examined the synergistic effect of ?9 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 (>25 mm 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 ?9 integrin or kindlin-1 alone promoted much less regeneration and recovery

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Cheah et al. full manuscript (Revised 04.05.16.pdf - Accepted Manuscript
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Accepted/In Press date: 30 May 2016
e-pub ahead of print date: 6 July 2016
Organisations: Biomedicine

Identifiers

Local EPrints ID: 404973
URI: https://eprints.soton.ac.uk/id/eprint/404973
PURE UUID: e5ac916e-a1dc-4acb-9a1d-419b213f27c6
ORCID for Melissa Andrews: ORCID iD orcid.org/0000-0001-5960-5619

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Date deposited: 25 Jan 2017 14:48
Last modified: 06 Jun 2018 12:14

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