Louie Allison Y, Drnevich Jenny, Johnson Jennifer L, Woodard Meagan, Kukekova Anna V, Johnson Rodney W, Steelman Andrew J
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
iScience. 2024 Jul 5;27(8):110464. doi: 10.1016/j.isci.2024.110464. eCollection 2024 Aug 16.
Peripheral viral infection disrupts oligodendrocyte (OL) homeostasis such that endogenous remyelination may be affected. Here, we demonstrate that influenza A virus infection perpetuated a demyelination- and disease-associated OL phenotype following cuprizone-induced demyelination that resulted in delayed OL maturation and remyelination in the prefrontal cortex. Furthermore, we assessed cellular metabolism , and found that infection altered brain OL and microglia metabolism in a manner that opposed the metabolic profile induced by remyelination. Specifically, infection increased glycolytic capacity of OLs and microglia, an effect that was recapitulated by lipopolysaccharide (LPS) stimulation of mixed glia cultures. In contrast, mitochondrial dependence was increased in OLs during remyelination, which was similarly observed in OLs of myelinating P14 mice compared to adult and aged mice. Collectively, our data indicate that respiratory viral infection is capable of suppressing remyelination, and suggest that metabolic dysfunction of OLs is implicated in remyelination impairment.
外周病毒感染会破坏少突胶质细胞（OL）的稳态，从而可能影响内源性髓鞘再生。在此，我们证明甲型流感病毒感染在铜离子载体诱导的脱髓鞘后使与脱髓鞘和疾病相关的OL表型持续存在，这导致前额叶皮质中OL成熟和髓鞘再生延迟。此外，我们评估了细胞代谢，发现感染以与髓鞘再生诱导的代谢谱相反的方式改变了脑OL和小胶质细胞的代谢。具体而言，感染增加了OL和小胶质细胞的糖酵解能力，脂多糖（LPS）刺激混合胶质细胞培养物也产生了类似的效果。相比之下，在髓鞘再生过程中OL的线粒体依赖性增加，在髓鞘形成的P14小鼠的OL中也观察到了类似情况，而成体和老年小鼠则不然。总体而言，我们的数据表明呼吸道病毒感染能够抑制髓鞘再生，并提示OL的代谢功能障碍与髓鞘再生受损有关。
