Kim Jin Hee, Yu Ji Eun, Chang Byung-Joon, Nahm Sang-Soep
Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
J Vet Sci. 2018 Nov 30;19(6):750-758. doi: 10.4142/jvs.2018.19.6.750.
Influenza virus infection is a zoonosis that has great socioeconomic effects worldwide. Influenza infection induces respiratory symptoms, while the influenza virus can infect brain and leave central nervous system sequelae. As children are more vulnerable to infection, they are at risk of long-term neurological effects once their brains are infected. We previously demonstrated that functional changes in hippocampal neurons were observed in mice recovered from neonatal influenza infection. In this study, we investigated changes in myelination properties that could affect neural dysfunction. Mice were infected with the influenza virus on postnatal day 5. Tissues were harvested from recovered mice 21-days post-infection. The expression levels for myelin basic protein (MBP) were determined, and immunohistochemical staining and transmission electron microscopy were performed. Real-time polymerase chain reaction and Western blot analyses showed that mRNA and protein expressions increased in the hippocampus and cerebellum of recovered mice. Increased MBP-staining signal was observed in the recovered mouse brain. By calculating the relative thickness of myelin sheath in relation to nerve fiber diameter (G-ratio) from electron photomicrographs, an increased G-ratio was observed in both the hippocampus and cerebellum of recovered mice. Influenza infection in oligodendrocyte-enriched primary brain cell cultures showed that proinflammatory cytokines may induce MBP upregulation. These results suggested that increased MBP expression could be a compensatory change related to hypomyelination, which may underlie neural dysfunction in recovered mice. In summary, the present results demonstrate that influenza infection during the neonatal period affects myelination and further induces functional changes in influenza-recovered mouse brain.
流感病毒感染是一种人畜共患病，在全球范围内具有重大的社会经济影响。流感感染会引发呼吸道症状，而流感病毒可感染大脑并留下中枢神经系统后遗症。由于儿童更容易受到感染，一旦他们的大脑被感染，就有长期神经功能影响的风险。我们之前证明，在从新生儿流感感染中恢复的小鼠中观察到海马神经元的功能变化。在本研究中，我们调查了可能影响神经功能障碍的髓鞘形成特性的变化。在出生后第5天给小鼠感染流感病毒。在感染后21天从恢复的小鼠中采集组织。测定髓鞘碱性蛋白（MBP）的表达水平，并进行免疫组织化学染色和透射电子显微镜检查。实时聚合酶链反应和蛋白质印迹分析表明，恢复小鼠的海马和小脑中mRNA和蛋白质表达增加。在恢复的小鼠大脑中观察到MBP染色信号增加。通过从电子显微照片计算髓鞘厚度与神经纤维直径的相对比值（G比值），发现恢复小鼠的海马和小脑中G比值均增加。在富含少突胶质细胞的原代脑细胞培养物中进行流感感染表明，促炎细胞因子可能诱导MBP上调。这些结果表明，MBP表达增加可能是与髓鞘形成不足相关的一种代偿性变化，这可能是恢复小鼠神经功能障碍的基础。总之，目前的结果表明，新生儿期的流感感染会影响髓鞘形成，并进一步诱导流感恢复小鼠大脑的功能变化。
