SUMMARY:
This article is protected by copyright. All rights reserved.
TITLE:
Macrophages influence Schwann cell myelin autophagy after nerve injury and in a model of Charcot-Marie-Tooth disease
DESCRIPTION:
BACKGROUND AND AIMS: The complex cellular and molecular interactions between Schwann cells and macrophages during Wallerian degeneration are a prerequisite to allow rapid uptake and degradation of myelin debris and axonal regeneration after peripheral nerve injury. In contrast, in non-injured nerves of Charcot-Marie-Tooth 1 neuropathies, aberrant macrophage activation by Schwann cells carrying myelin gene defects is a disease amplifier that drives nerve damage and subsequent functional decline….
CONTENT:
J Peripher Nerv Syst. 2023 May 20. doi: 10.1111/jns.12561. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: The complex cellular and molecular interactions between Schwann cells and macrophages during Wallerian degeneration are a prerequisite to allow rapid uptake and degradation of myelin debris and axonal regeneration after peripheral nerve injury. In contrast, in non-injured nerves of Charcot-Marie-Tooth 1 neuropathies, aberrant macrophage activation by Schwann cells carrying myelin gene defects is a disease amplifier that drives nerve damage and subsequent functional decline. Consequently, targeting nerve macrophages might be a translatable treatment strategy to mitigate disease outcome in CMT1 patients. Indeed, in previous approaches, macrophage targeting alleviated the axonopathy and promoted sprouting of damaged fibers. Surprisingly, this was still accompanied by robust myelinopathy in a model for CMT1X, suggesting additional cellular mechanisms of myelin degradation in mutant peripheral nerves. We here investigated the possibility of an increased Schwann cell-related myelin autophagy upon macrophage targeting in Cx32def mice.
METHODS: Combining ex vivo and in vivo approaches, macrophages were targeted by PLX5622 treatment. Schwann cell autophagy was investigated by immunohistochemical and electron microscopical techniques.
RESULTS: We demonstrate a robust upregulation of markers for Schwann cell autophagy after injury and in genetically-mediated neuropathy when nerve macrophages are pharmacologically depleted. Corroborating these findings, we provide ultrastructural evidence for increased Schwann cell myelin autophagy upon treatment in vivo.
INTERPRETATION: These findings reveal a novel communication and interaction between Schwann cells and macrophages. This identification of alternative pathways of myelin degradation may have important implications for a better understanding of therapeutic mechanisms of pharmacological macrophage targeting in diseased peripheral nerves. This article is protected by copyright. All rights reserved.
PMID:37209383 | DOI:10.1111/jns.12561
SOURCE:
Journal of the peripheral nervous system : JPNS
TAGS:
This article is protected by copyright All rights reserved
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2023-05-20T16:13:31Z
DATE – DOI: 2023-05-20T16:13:31Z
DATE – PUBMED: 2023 May 20
DATE OUTPUT MATCHED: True
DATE – ADDED:
Sat, 20 May 2023 06:00:00 -0400
DATE – RETRIEVED:
05/20/23 07:09PM
2023-05-20T19:09:58-04:00
FEATURED IMAGE:
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IDENTIFIER:
pmid:37209383,doi:10.1111/jns.12561
PUBMED ID:
pubmed:37209383
DOI:
10.1111/jns.12561
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37209383/
LINK – DOI:
https://doi.org/10.1111/jns.12561
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1111/jns.12561
REFERENCES:
CMT Treatment Report, Urgent Research, 2023-05-20T19:09:58-04:00, https://www.cmttreatmentreport.com.
