{"title":"间充质干细胞细胞外囊泡传递的MiR-124通过稳定大鼠脊髓损伤后p62-Keap1-Nrf2通路发挥神经保护作用","authors":"Chao Fang, Jun Qian, Bi-Zhi Tu, Xiang Xia, Chong-Yu Jia, Cai-Liang Shen","doi":"10.1007/s12035-025-04755-2","DOIUrl":null,"url":null,"abstract":"<p><p>Spinal cord injury (SCI) can cause irreversible trauma to nervous tissue, leading to permanent damage to the patient's motor and sensory functions. Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) can simulate most of the functions of MSCs and are considered an ideal treatment option for SCI. However, the potential mechanism of MSC-EVs treatment for SCI still needs to be explored. We cultured neurons in vitro to investigate the effect of miR-124 on the p62-Keap1-Nrf2 pathway. Besides, MSC-EVs containing miR-124 were injected into a rat spinal cord injury model to observe their neural repair effect. The accumulation of p62 can be reversed by miR-124, which promotes autophagy and alleviates oxidative stress, thereby exerting neuroprotective effects. Rats who received injection of MSC-EVs overexpressing miR-124 after surgery showed higher BBB scores, lower levels of cell apoptosis, and better spinal cord tissue morphology. Our results indicated that miR-124 can stabilize the p62-Keap1-Nrf2 loop, thereby promoting autophagy and alleviating oxidative stress to exert neuroprotective effects. Our research proposes a novel potential target for treating SCI.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8328-8340"},"PeriodicalIF":4.6000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208983/pdf/","citationCount":"0","resultStr":"{\"title\":\"MiR-124 Delivered by Extracellular Vesicles from Mesenchymal Stem Cell Exerts Neuroprotective Effects by Stabilizing the p62-Keap1-Nrf2 Pathway after Spinal Cord Injury in Rats.\",\"authors\":\"Chao Fang, Jun Qian, Bi-Zhi Tu, Xiang Xia, Chong-Yu Jia, Cai-Liang Shen\",\"doi\":\"10.1007/s12035-025-04755-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Spinal cord injury (SCI) can cause irreversible trauma to nervous tissue, leading to permanent damage to the patient's motor and sensory functions. Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) can simulate most of the functions of MSCs and are considered an ideal treatment option for SCI. However, the potential mechanism of MSC-EVs treatment for SCI still needs to be explored. We cultured neurons in vitro to investigate the effect of miR-124 on the p62-Keap1-Nrf2 pathway. Besides, MSC-EVs containing miR-124 were injected into a rat spinal cord injury model to observe their neural repair effect. The accumulation of p62 can be reversed by miR-124, which promotes autophagy and alleviates oxidative stress, thereby exerting neuroprotective effects. Rats who received injection of MSC-EVs overexpressing miR-124 after surgery showed higher BBB scores, lower levels of cell apoptosis, and better spinal cord tissue morphology. Our results indicated that miR-124 can stabilize the p62-Keap1-Nrf2 loop, thereby promoting autophagy and alleviating oxidative stress to exert neuroprotective effects. Our research proposes a novel potential target for treating SCI.</p>\",\"PeriodicalId\":18762,\"journal\":{\"name\":\"Molecular Neurobiology\",\"volume\":\" \",\"pages\":\"8328-8340\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208983/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Neurobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12035-025-04755-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12035-025-04755-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
MiR-124 Delivered by Extracellular Vesicles from Mesenchymal Stem Cell Exerts Neuroprotective Effects by Stabilizing the p62-Keap1-Nrf2 Pathway after Spinal Cord Injury in Rats.
Spinal cord injury (SCI) can cause irreversible trauma to nervous tissue, leading to permanent damage to the patient's motor and sensory functions. Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) can simulate most of the functions of MSCs and are considered an ideal treatment option for SCI. However, the potential mechanism of MSC-EVs treatment for SCI still needs to be explored. We cultured neurons in vitro to investigate the effect of miR-124 on the p62-Keap1-Nrf2 pathway. Besides, MSC-EVs containing miR-124 were injected into a rat spinal cord injury model to observe their neural repair effect. The accumulation of p62 can be reversed by miR-124, which promotes autophagy and alleviates oxidative stress, thereby exerting neuroprotective effects. Rats who received injection of MSC-EVs overexpressing miR-124 after surgery showed higher BBB scores, lower levels of cell apoptosis, and better spinal cord tissue morphology. Our results indicated that miR-124 can stabilize the p62-Keap1-Nrf2 loop, thereby promoting autophagy and alleviating oxidative stress to exert neuroprotective effects. Our research proposes a novel potential target for treating SCI.
期刊介绍：
Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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