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Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain.
Tang, Yidan; Wu, Jiahui; Liu, Changliang; Gan, Lu; Chen, Hai; Sun, Ya-Lan; Liu, Jin; Tao, Yuan-Xiang; Zhu, Tao; Chen, Chan.
Afiliación
  • Tang Y; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Wu J; Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Liu C; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Gan L; Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Chen H; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Sun YL; Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Liu J; Research Laboratory of Emergency Medicine, West China Hospital, Emergency Medicine and National Clinical Research Center for Geriatrics, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Tao YX; Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Zhu T; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • Chen C; Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
J Neuroinflammation ; 21(1): 99, 2024 Apr 17.
Article en En | MEDLINE | ID: mdl-38632655
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Vesículas Extracelulares / Neuralgia Límite: Animals Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Vesículas Extracelulares / Neuralgia Límite: Animals Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido