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Neonatal influenza virus infection affects myelination in the recovered mouse brain
Jin Hee Kim, Ji Eun Yu, Byung-Joon Chang, Sang-Soep Nahm*
Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University Seoul 05029, Korea
Correspondence to: Tel: +82-2-450-3705; Fax: +82-2-450-3037; E-mail: ssnahm@konkuk.ac.kr
Received: April 24, 2018; Revised: July 24, 2018; Accepted: August 6, 2018; Published online: August 30, 2018.
Abstract
Influenza virus infection is a zoonosis that has great socioeconomic impact worldwide. Influenza infection induces respiratory symptoms, while influenza virus can infect brain and leave CNS 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 the 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 PCR and Western blot analyses showed that mRNA and protein expression 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, 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 the up-regulation of MBP. These results suggested that increased MBP expression could be a compensatory change due to hypomyelination, which may underlie neural dysfunction in the recovered mice. In summary, the present results demonstrated that influenza infection during the neonatal period affects myelination and further induces functional changes in the recovered mouse brain.
Keywords: influenza, cerebellum, hippocampus, myelin, oligodendrocyte


© 2018 The Korean Society of Veterinary Science.