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- Title
Reassembly of Excitable Domains after CNS Axon Regeneration.
- Authors
Marin, Miguel A.; de Lima, Silmara; Gilbert, Hui-Ya; Giger, Roman J.; Benowitz, Larry; Rasband, Matthew N.
- Abstract
Action potential initiation and propagation in myelinated axons require ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Disruption of these domains after injury impairs nervous system function. Traditionally, injured CNS axons are considered refractory to regeneration, but some recent approaches challenge this view by showing robust long-distance regeneration. However, whether these approaches allow remyelination and promote the reestablishment of AIS and nodes of Ranvier is unknown. Using mouse optic nerve crush as a model for CNS traumatic injury, we performed a detailed analysis of AIS and node disruption after nerve crush. We found significant disruption of AIS and loss of nodes within days of the crush, and complete loss of nodes 1 week after injury. Genetic deletion of the tumor suppressor phosphatase and tensin homolog (Pten) in retinal ganglion cells (RGCs), coupled with stimulation of RGCs by inflammation and cAMP, dramatically enhanced regeneration. With this treatment, we found significant reestablishment of RGCAIS, remyelination, and even reassembly of nodes in regions proximal, within, and distal to the crush site. Remyelination began near the retina, progressed distally, and was confirmed by electron microscopy. Although axons grew rapidly, remyelination and nodal ion channel clustering was much slower. Finally, genetic deletion of ankyrinG from RGCs to block AIS reassembly did not affect axon regeneration, indicating that preservation of neuronal polarity is not required for axon regeneration. Together, our results demonstrate, for the first time, that regenerating CNS axons can be remyelinated and reassemble new AIS and nodes of Ranvier.
- Subjects
CENTRAL nervous system; RETINAL ganglion cells; AXONS; NODES of Ranvier; ELECTRON microscopy
- Publication
Journal of Neuroscience, 2016, Vol 36, Issue 35, p9148
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1747-16.2016