Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury

Di Wu, Ying Jin, Tatiana M. Shapiro, Abhishek Hinduja, Peter W. Baas and Veronica J. Tom ()
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Di Wu: Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine
Ying Jin: Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine
Tatiana M. Shapiro: Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine
Abhishek Hinduja: Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine
Peter W. Baas: Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine
Veronica J. Tom: Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract After a dorsal root crush injury, centrally-projecting sensory axons fail to regenerate across the dorsal root entry zone (DREZ) to extend into the spinal cord. We find that chemogenetic activation of adult dorsal root ganglion (DRG) neurons improves axon growth on an in vitro model of the inhibitory environment after injury. Moreover, repeated bouts of daily chemogenetic activation of adult DRG neurons for 12 weeks post-crush in vivo enhances axon regeneration across a chondroitinase-digested DREZ into spinal gray matter, where the regenerating axons form functional synapses and mediate behavioral recovery in a sensorimotor task. Neuronal activation-mediated axon extension is dependent upon changes in the status of tubulin post-translational modifications indicative of highly dynamic microtubules (as opposed to stable microtubules) within the distal axon, illuminating a novel mechanism underlying stimulation-mediated axon growth. We have identified an effective combinatory strategy to promote functionally-relevant axon regeneration of adult neurons into the CNS after injury.

Date: 2020
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DOI: 10.1038/s41467-020-19914-3

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