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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

01-12-2022 | Neuropathic Pain | Research

LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice

Authors: Chaitanya K. Gavini, Nadia Elshareif, Gregory Aubert, Anand V. Germanwala, Nigel A. Calcutt, Virginie Mansuy-Aubert

Published in: Journal of Neuroinflammation | Issue 1/2022

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Abstract

Background

Peripheral neuropathy is a common and progressive disorder in the elderly that interferes with daily activities. It is of importance to find efficient treatments to treat or delay this age-related neurodegeneration. Silencing macrophages by reducing foamy macrophages showed significant improvement of age-related degenerative changes in peripheral nerves of aged mice. We previously demonstrated that activation of the cholesterol sensor Liver X receptor (LXR) with the potent agonist, GW3965, alleviates pain in a diet-induced obesity model. We sought to test whether LXR activation may improve neuropathy in aged mice.

Methods

21-month-old mice were treated with GW3965 (25 mg/Kg body weight) for 3 months while testing for mechanical allodynia and thermal hyperalgesia. At termination, flow cytometry was used to profile dorsal root ganglia and sciatic nerve cells. Immune cells were sorted and analyzed for cholesterol and gene expression. Nerve fibers of the skin from the paws were analyzed. Some human sural nerves were also evaluated. Comparisons were made using either t test or one-way ANOVA.

Results

Treatment with GW3965 prevented the development of mechanical hypersensitivity and thermal hyperalgesia over time in aged mice. We also observed change in polarization and cholesterol content of sciatic nerve macrophages accompanied by a significant increase in nerve fibers of the skin.

Conclusions

These results suggest that activation of the LXR may delay the PNS aging by modifying nerve-immune cell lipid content. Our study provides new potential targets to treat or delay neuropathy during aging.
Appendix
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Metadata
Title
LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice
Authors
Chaitanya K. Gavini
Nadia Elshareif
Gregory Aubert
Anand V. Germanwala
Nigel A. Calcutt
Virginie Mansuy-Aubert
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-022-02423-z

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