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Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury
- Source :
- Nature Communications, Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020)
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group UK, 2020.
-
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.<br />Central axons have limited regenerative ability following injury. Here, the authors show that chronic activation of DRG neurons results in highly dynamic microtubules at the distal axons and enhanced axonal regrowth and synaptogenesis in the spinal cord affecting functional recovery.
- Subjects :
- 0301 basic medicine
Science
General Physics and Astronomy
Sensory system
Inhibitory postsynaptic potential
Microtubules
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Crush Injuries
0302 clinical medicine
Dorsal root ganglion
Ganglia, Spinal
medicine
Animals
Axon
Rats, Wistar
Regeneration and repair in the nervous system
Clozapine
Neurons
Multidisciplinary
biology
Axon extension
General Chemistry
medicine.disease
Spinal cord
Cellular neuroscience
Axons
Nerve Regeneration
Rats
030104 developmental biology
medicine.anatomical_structure
Tubulin
nervous system
Spinal Cord
biology.protein
Crush injury
Female
Spinal Nerve Roots
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....05bf9392d3bea34f70b766d1ce025cad