星形胶质细胞外泌体转运的 miRNA-26a-5p 可改善七氟醚诱导的老年小鼠认知功能障碍

IF 6.4 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Translational Research Pub Date : 2024-01-19 DOI:10.1016/j.trsl.2024.01.007
Junhua Li , Hui Xu , Kun Zhang , Yafang Liu , Cong Zeng , Yanni Fu , Yujuan Li
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引用次数: 0

摘要

长时间的七氟烷麻醉是导致围手术期神经认知障碍(PND)的主要因素。最近的研究强调,神经元凋亡和树突结构异常是 PND 的关键特征。星形胶质细胞衍生的外泌体(ADEs)已被确定为微RNAs(miRNAs)的载体,通过传递遗传物质在细胞间通信中发挥着重要作用。然而,ADEs中的miRNA如何导致七氟醚诱导的认知缺陷的具体机制目前尚不清楚。通过一系列体内和体外实验,我们证明了 ADEs 通过减少神经元凋亡和促进树突发育来改善神经认知结果。我们的 miRNA 微阵列分析表明,在 ADEs 中,miR-26a-5p 的表达水平显著增加。此外,我们还发现 NCAM 是 miR-26a-5p 的下游靶基因。随后进行的功能增益和功能缺失实验验证了 miR-26a-5p/NCAM 轴的作用。最后,我们发现 AKT/GSK3-β/CRMP2 信号通路参与了通过外泌体 miR-26a-5p 调节神经元的过程。综上所述,我们的研究结果表明,用miR-26a-5p治疗ADEs可改善长期七氟醚麻醉诱导的神经认知结果,为延缓PND的进展提供了一种可行的方法。
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Astrocyte-derived exosomes-transported miRNA-26a-5p ameliorates sevoflurane-induced cognitive dysfunction in aged mice

Prolonged sevoflurane anesthesia is the primary factor contributing to the development of perioperative neurocognitive disorders (PND). Recent studies have highlighted neuronal apoptosis and abnormal dendritic structures as crucial features of PND. Astrocytes-derived exosomes (ADEs) have been identified as carriers of microRNAs (miRNAs), playing a vital role in cell-to-cell communication through transmitting genetic material. Nevertheless, the specific mechanisms by which miRNAs in ADEs contribute to sevoflurane-induced cognitive deficit are currently unknown. Through a series of in vivo and in vitro experiments, we demonstrated that ADEs contributed to improved neurocognitive outcomes by reducing neuronal apoptosis and promoting dendritic development. Our miRNA microarray analysis revealed a significant increase in the expression level of miR-26a-5p within ADEs. Furthermore, we identified NCAM as the downstream target gene of miR-26a-5p. Subsequent gain- and loss-of-function experiments were conducted to validate the role of the miR-26a-5p/NCAM axis. Finally, we found that the AKT/GSK3-β/CRMP2 signaling pathway was involved in regulating neurons through exosomal miR-26a-5p. Taken together, our findings suggest that the treatment with miR-26a-5p in ADEs can improve neurocognitive outcomes induced by long-term sevoflurane anesthesia, suggesting a promising approach for retarding the progress of PND.

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来源期刊
Translational Research
Translational Research 医学-医学:内科
CiteScore
15.70
自引率
0.00%
发文量
195
审稿时长
14 days
期刊介绍: Translational Research (formerly The Journal of Laboratory and Clinical Medicine) delivers original investigations in the broad fields of laboratory, clinical, and public health research. Published monthly since 1915, it keeps readers up-to-date on significant biomedical research from all subspecialties of medicine.
期刊最新文献
Contents Contents Masthead Lympho-myeloid aggregate-infiltrating CD20+ B cells display a double-negative phenotype and correlate with poor prognosis in esophageal squamous cell carcinoma Editorial Advisory Board
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