Skip to content

Research at St Andrews

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

Research output: Research - peer-reviewArticle

DOI

Open Access permissions

Open

Author(s)

Menghon Cheah, Melissa Renee Andrews, Daniel Chew, Elizabeth Moloney, Joost Verhaagen, Reinhard Fassler, James Fawcett

School/Research organisations

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.
Close

Details

Original languageEnglish
Pages (from-to)7283-7297
Number of pages15
JournalThe Journal of Neuroscience
Volume36
Issue number27
DOIs
StatePublished - 6 Jul 2016

    Research areas

  • Adeno-associated virus , Alpha9 integrin, Axon regeneration, Dorsal root ganglion, Kindlin-1, Spinal cord

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Wide-Field Multiphoton Imaging Through Scattering Media

    Escobet-Montalbán, A., Spesyvtsev, R., Chen, M., Saber, W. A., Andrews, M., Herrington, C. S., Mazilu, M. & Dholakia, K. 20 Dec 2017 In : ArXiv e-prints.

    Research output: ResearchArticle

  2. Integrated single- and two-photon light sheet microscopy using accelerating beams

    Piksarv, P., Marti, D., Le, T., Unterhuber, A., Forbes, L. H., Andrews, M. R., Stingl, A., Drexler, W., Andersen, P. E. & Dholakia, K. 3 May 2017 In : Scientific Reports. 7, 1435

    Research output: Research - peer-reviewArticle

  3. Targeting cell surface receptors for axon regeneration in the central nervous system

    Cheah, M. & Andrews, M. R. 5 Jan 2017 In : Neural Regeneration Research. 11, 12, p. 1884-1887 4 p.

    Research output: Research - peer-reviewReview article

Related by journal

  1. Sodium pumps mediate activity-dependent changes in mammalian motor networks

    Picton, L. D., Nascimento, F., Broadhead, M. J., Sillar, K. T. & Miles, G. B. 25 Jan 2017 In : The Journal of Neuroscience. 37, 4, p. 906-921 16 p.

    Research output: Research - peer-reviewArticle

  2. Selective gating of neuronal activity by intrinsic properties in distinct motor rhythms

    Li, W. 8 Jul 2015 In : The Journal of Neuroscience. 35, 27, p. 9799-9810

    Research output: Research - peer-reviewArticle

  3. Deep brain stimulation of different pedunculopontine targets in a novel rodent model of parkinsonism

    Gut, N. K. & Winn, P. 25 Mar 2015 In : The Journal of Neuroscience. 35, 12, p. 4792-4803 12 p.

    Research output: Research - peer-reviewArticle

  4. The generation of antiphase oscillations and synchrony by a rebound-based vertebrate central pattern generator

    Li, W., Merrison-Hort, R., Zhang, H. Y. & Borisyuk, R. 23 Apr 2014 In : The Journal of Neuroscience. 34, 17, p. 6065-77 13 p.

    Research output: Research - peer-reviewArticle

ID: 243606485