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

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Author(s)

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

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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.
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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

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