Influenza A virus infection disrupts oligodendrocyte homeostasis and alters the myelin lipidome in the adult mouse.
Influenza A virus infection disrupts oligodendrocyte homeostasis and alters the myelin lipidome in the adult mouse.
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DOI：
10.1186/s12974-023-02862-2
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发表时间：
2023-08-19
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
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作者：
最近的数据表明，髓鞘可能会被中枢神经系统外发生的生理事件改变，这可能会导致认知和行为的变化。同样，非嗜神经性病毒的外周感染也会引起认知和行为的变化。小鼠接种生理盐水或甲型流感病毒。使用批量RNA-seq、脂质组学、RT-qPCR、流式细胞术、免疫染色和蛋白质印迹来确定感染对OL活力、蛋白质表达和脂质组变化的影响。为了确定小胶质细胞是否介导感染诱导的OL稳态变化，用小胶质细胞活化抑制剂GW 2580处理小鼠。此外，使用原代胶质细胞培养物的条件培养基实验也用于测试来自小胶质细胞的分泌因子是否可以抑制OL基因表达。转录组学和RT-qPCR分析显示OL特异性转录物的时间下调，同时细胞应激标志物的特征性上调。与盐水接种对照组相比，从感染小鼠中分离的OL的髓鞘蛋白的细胞表达减少。相反，这些蛋白质在髓鞘内的表达在组间没有差异。类似地，对不同脑区进行的组织学和免疫印迹分析表明，感染并没有改变OL活力，但增加了细胞应激标志物的表达。鸟枪脂质组学分析显示，感染改变了前额叶皮层以及纯化的脑髓鞘内的脂质分布，并且这些变化在感染恢复后持续存在。在感染期间用GW 2580治疗抑制了与胶质细胞活化相关的基因的表达，并将OL特异性转录物部分恢复到基线水平。最后，从激活的小胶质细胞的条件培养基降低OL-基因表达的主要OL不改变他们的生存能力。这些发现表明，外周呼吸道病毒感染IAV能够改变OL稳态，并表明小胶质细胞活化可能参与了这一过程。在线版本包含补充材料，可通过10.1186/s12974-023-02862-2获得。
Recent data suggest that myelin may be altered by physiological events occurring outside of the central nervous system, which may cause changes to cognition and behavior. Similarly, peripheral infection by non-neurotropic viruses is also known to evoke changes to cognition and behavior. Mice were inoculated with saline or influenza A virus. Bulk RNA-seq, lipidomics, RT-qPCR, flow cytometry, immunostaining, and western blots were used to determine the effect of infection on OL viability, protein expression and changes to the lipidome. To determine if microglia mediated infection-induced changes to OL homeostasis, mice were treated with GW2580, an inhibitor of microglia activation. Additionally, conditioned medium experiments using primary glial cell cultures were also used to test whether secreted factors from microglia could suppress OL gene expression. Transcriptomic and RT-qPCR analyses revealed temporal downregulation of OL-specific transcripts with concurrent upregulation of markers characteristic of cellular stress. OLs isolated from infected mice had reduced cellular expression of myelin proteins compared with those from saline-inoculated controls. In contrast, the expression of these proteins within myelin was not different between groups. Similarly, histological and immunoblotting analysis performed on various brain regions indicated that infection did not alter OL viability, but increased expression of a cellular stress marker. Shot-gun lipidomic analysis revealed that infection altered the lipid profile within the prefrontal cortex as well as in purified brain myelin and that these changes persisted after recovery from infection. Treatment with GW2580 during infection suppressed the expression of genes associated with glial activation and partially restored OL-specific transcripts to baseline levels. Finally, conditioned medium from activated microglia reduced OL-gene expression in primary OLs without altering their viability. These findings show that peripheral respiratory viral infection with IAV is capable of altering OL homeostasis and indicate that microglia activation is likely involved in the process. The online version contains supplementary material available at 10.1186/s12974-023-02862-2.
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影响因子：
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作者：
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影响因子：
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