Axo‐glial interaction in the injured PNS

Stassart, Ruth M.

doi:10.1002/dneu.22771

Cited by 27 publications

(30 citation statements)

References 155 publications

(255 reference statements)

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“…After this initial regression to the progenitor-like cell, SCs activate different molecular mechanisms to eventually transform into the regeneration-supporting phenotype. Through this process, SCs will acquire the new identity of repair SCs [ 10 , 20 , 21 , 22 , 23 , 24 ]. The regression to a progenitor-like cell phase is characterized by a reversal of all developmental steps that assist SCs during the functional acquisition of tools for proper interactions with axons.…”

Section: Phase One: Detachment From Degenerating Axons—denervationmentioning

confidence: 99%

“…Of the three members of the neuregulin-1 family, NRG-1 type III plays an essential role in SC proliferation, differentiation and myelination during development and in the remyelination of regenerating nerves [ 24 , 46 , 48 , 115 ]. Interestingly, in vivo experiments in mice after severe crushed nerve lesions demonstrated that an overexpression of NRG-1 type III can restore the correct thickness of myelin.…”

Section: Phase Four: Contact With Regrowth Axonsmentioning

confidence: 99%

“…Interestingly, in vivo experiments in mice after severe crushed nerve lesions demonstrated that an overexpression of NRG-1 type III can restore the correct thickness of myelin. However, it can also induce hypermyelination [ 24 , 66 ]. In addition, this study demonstrated that, similarly to NRG-I type III, the overexpression of NRG1 type I also allows for the proper restoration of the myelin sheath of regenerating adult nerves.…”

Section: Phase Four: Contact With Regrowth Axonsmentioning

confidence: 99%

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Dynamic Environmental Physical Cues Activate Mechanosensitive Responses in the Repair Schwann Cell Phenotype

Fornaro

Marcus

Rattin

et al. 2021

Cells

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Schwann cells plastically change in response to nerve injury to become a newly reconfigured repair phenotype. This cell is equipped to sense and interact with the evolving and unusual physical conditions characterizing the injured nerve environment and activate intracellular adaptive reprogramming as a consequence of external stimuli. Summarizing the literature contributions on this matter, this review is aimed at highlighting the importance of the environmental cues of the regenerating nerve as key factors to induce morphological and functional changes in the Schwann cell population. We identified four different microenvironments characterized by physical cues the Schwann cells sense via interposition of the extracellular matrix. We discussed how the physical cues of the microenvironment initiate changes in Schwann cell behavior, from wrapping the axon to becoming a multifunctional denervated repair cell and back to reestablishing contact with regenerated axons.

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Section: Phase One: Detachment From Degenerating Axons—denervationmentioning

confidence: 99%

Section: Phase Four: Contact With Regrowth Axonsmentioning

confidence: 99%

Section: Phase Four: Contact With Regrowth Axonsmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic Environmental Physical Cues Activate Mechanosensitive Responses in the Repair Schwann Cell Phenotype

Fornaro

Marcus

Rattin

et al. 2021

Cells

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“…The molecular mechanisms of Schwann cell remyelination share similarities to myelination during development, however there are also notable differences (Stassart & Woodhoo, 2020). Given the role of class II a HDACs in myelination we asked whether they are also involved in remyelination after nerve injury.…”

Section: Remyelination Kinetics Depends On Class Iia Hdac Gene Dosementioning

confidence: 99%

“…After axon regeneration Schwann cells reestablish contact with them and downregulate c-Jun. This allows re-expression of Krox20 and the consequent reactivation of a gene expression program aimed at remyelination of axons and reestablishment of nerve function (Stassart & Woodhoo, 2020). Activation of Gpr126, a G-protein-coupled receptor that increases intracellular levels of cAMP, is required for Schwann cell myelination and remyelination (Monk et al, 2009(Monk et al, , 2011.…”

Section: Introductionmentioning

confidence: 99%

A genetic compensatory mechanism regulated by c-Jun and Mef2d modulates the expression of distinct class IIa HDACs to ensure peripheral nerve myelination and repair

Cabedo

Velasco-Aviles

Patel

et al. 2021

Preprint

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The class IIa histone-deacetylases (HDACs) have pivotal roles in the development of different tissues. Of this family, Schwann cells express HDAC4, 5 and 7 but not HDCA9. Here we show that a transcription factor regulated genetic compensatory mechanism within this family of proteins, blocks negative regulators of myelination ensuring peripheral nerve developmental myelination and remyelination after injury. Thus, when HDAC4 and 5 are knocked-out from Schwann cells, a c-Jun dependent mechanism induces the compensatory overexpression of HDAC7 permitting, although with a delay, the formation of a myelin sheath. When HDAC4,5 and 7 are simultaneously removed, the Myocyte- specific enhancer-factor d (Mef2d) binds to the promoter and induces the de novo expression of HDAC9, and although several melanocytic- lineage genes are mis- expressed and Remak bundle structure is disrupted, myelination proceeds after a long delay. Thus, our data unveil a finely tuned compensatory mechanism within the class IIa HDAC family, coordinated by distinct transcription factors, that guarantees the ability of Schwann cells to myelinate during development and remyelinate after nerve injury.

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Myelinated peripheral axons are more vulnerable to mechanical trauma in a model of enlarged axonal diameters

Gargareta,

Berghoff,

Krauter

et al. 2024

Glia

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The velocity of axonal impulse propagation is facilitated by myelination and axonal diameters. Both parameters are frequently impaired in peripheral nerve disorders, but it is not known if the diameters of myelinated axons affect the liability to injury or the efficiency of functional recovery. Mice lacking the adaxonal myelin protein chemokine‐like factor‐like MARVEL‐transmembrane domain‐containing family member‐6 (CMTM6) specifically from Schwann cells (SCs) display appropriate myelination but increased diameters of peripheral axons. Here we subjected Cmtm6‐cKo mice as a model of enlarged axonal diameters to a mild sciatic nerve compression injury that causes temporarily reduced axonal diameters but otherwise comparatively moderate pathology of the axon/myelin‐unit. Notably, both of these pathological features were worsened in Cmtm6‐cKo compared to genotype‐control mice early post‐injury. The increase of axonal diameters caused by CMTM6‐deficiency thus does not override their injury‐dependent decrease. Accordingly, we did not detect signs of improved regeneration or functional recovery after nerve compression in Cmtm6‐cKo mice; depleting CMTM6 in SCs is thus not a promising strategy toward enhanced recovery after nerve injury. Conversely, the exacerbated axonal damage in Cmtm6‐cKo nerves early post‐injury coincided with both enhanced immune response including foamy macrophages and SCs and transiently reduced grip strength. Our observations support the concept that larger peripheral axons are particularly susceptible toward mechanical trauma.

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Axo‐glial interaction in the injured PNS

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 27 publications

References 155 publications

Dynamic Environmental Physical Cues Activate Mechanosensitive Responses in the Repair Schwann Cell Phenotype

Dynamic Environmental Physical Cues Activate Mechanosensitive Responses in the Repair Schwann Cell Phenotype

A genetic compensatory mechanism regulated by c-Jun and Mef2d modulates the expression of distinct class IIa HDACs to ensure peripheral nerve myelination and repair

Myelinated peripheral axons are more vulnerable to mechanical trauma in a model of enlarged axonal diameters

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