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.
Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury
Creators
Di Wu - Drexel University
Ying Jin - Drexel University
Tatiana M. Shapiro - Drexel University
Abhishek Hinduja - Drexel University
Peter W. Baas - Drexel University
Veronica J. Tom - Drexel University
Publication Details
Nature communications, v 11(1), pp 6131-6131
Publisher
Springer Nature
Number of pages
16
Grant note
259350 / Craig H. Neilsen Foundation
R01 NS085426; R01 NS106908; R01 NS111761; R01 NS28785; R01 NS118117 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
W81XWH1210379 / U.S. Army Medical Research and Materiel Command; U.S. Army Medical Research & Materiel Command (USAMRMC)
Resource Type
Journal article
Language
English
Academic Unit
Neurobiology and Anatomy
Web of Science ID
WOS:000617695100014
Scopus ID
2-s2.0-85096938819
Other Identifier
991019167603004721
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