PDF(Pubmed)
Abstract：
Extracellular vesicles (EVs) are released by all cells, can cross the blood-brain barrier, and have been shown to play an important role in cellular communication, substance shuttling, and immune modulation. In recent years EVs have shifted into focus in multiple sclerosis (MS) research as potential plasma biomarkers and therapeutic vehicles. Yet little is known about the disease-associated changes in EVs in the central nervous system (CNS). To address this gap, we characterized the physical and proteomic changes of mouse spinal cord-derived EVs before and at 16 and 25 days after the induction of experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory model of MS. Using various bioinformatic tools, we found changes in inflammatory, glial, and synaptic proteins and pathways, as well as a shift in the predicted contribution of immune and glial cell types over time. These results show that EVs provide snapshots of crucial disease processes such as CNS-compartmentalized inflammation, re/de-myelination, and synaptic pathology, and might also mediate these processes. Additionally, inflammatory plasma EV biomarkers previously identified in people with MS were also altered in EAE spinal cord EVs, suggesting commonalities of EV-related pathological processes during EAE and MS and overlap of EV proteomic changes between CNS and circulating EVs.
摘要：
细胞外囊泡（EV）由所有细胞释放，可以穿过血脑屏障，并被证明在细胞通信中发挥着重要作用，物质穿梭，和免疫调节。近年来，EV已成为多发性硬化症（MS）研究的焦点，作为潜在的血浆生物标志物和治疗载体。然而，关于中枢神经系统（CNS）中EV的疾病相关变化知之甚少。为了解决这个差距，我们表征了小鼠脊髓来源的EV在诱导实验性自身免疫性脑脊髓炎（EAE）之前和之后16天和25天的物理和蛋白质组学变化，MS的神经炎症模型使用各种生物信息学工具，我们发现炎症的变化，胶质,和突触蛋白和通路，以及免疫和神经胶质细胞类型的预测贡献随时间的变化。这些结果表明，电动汽车提供了关键疾病过程的快照，如中枢神经系统分隔的炎症，再/去髓鞘化，和突触病理学，也可能调解这些过程。此外,先前在MS患者中发现的炎性血浆EV生物标志物在EAE脊髓EV中也发生了改变，提示EAE和MS期间EV相关病理过程的共性以及CNS和循环EV之间EV蛋白质组变化的重叠。
