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Open Access 01-12-2024 | Neuropathic Pain | Research

Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain

Authors: Yidan Tang, Jiahui Wu, Changliang Liu, Lu Gan, Hai Chen, Ya-Lan Sun, Jin Liu, Yuan-Xiang Tao, Tao Zhu, Chan Chen

Published in: Journal of Neuroinflammation | Issue 1/2024

Abstract

Background

The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP.

Methods

We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p.

Results

The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats.

Conclusion

Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.

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Title: Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain
Authors: Yidan Tang
Jiahui Wu
Changliang Liu
Lu Gan
Hai Chen
Ya-Lan Sun
Jin Liu
Yuan-Xiang Tao
Tao Zhu
Chan Chen
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Neuropathic Pain
Published in: Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-024-03081-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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