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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Neonatal influenza virus infection affects myelination in influenza-recovered mouse brain
Jin Hee Kim1, Ji Eun Yu1, Byung-Joon Chang1
1Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
Insights
Neonatal influenza infection in mice led to altered brain myelination, evidenced by increased myelin basic protein (MBP) and changes in the G-ratio. These findings suggest a compensatory response to hypomyelination, potentially causing long-term neurological issues.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Influenza virus infection is a zoonotic disease with significant global socioeconomic impact.
- Central nervous system (CNS) sequelae can result from influenza virus brain infections, particularly in vulnerable children.
- Previous research indicated functional changes in hippocampal neurons following neonatal influenza infection.
Purpose of the Study:
- To investigate the impact of neonatal influenza infection on brain myelination properties in recovered mice.
- To determine if changes in myelination contribute to neural dysfunction after influenza infection.
- To explore the molecular mechanisms underlying altered myelination in response to influenza.
Main Methods:
- Neonatal mice were infected with influenza virus on postnatal day 5 and tissues were collected 21 days post-infection.
- Myelin basic protein (MBP) expression was analyzed using real-time PCR, Western blot, and immunohistochemistry.
- Transmission electron microscopy was used to assess myelination via G-ratio calculation.
- Oligodendrocyte-enriched primary brain cell cultures were used to study the effect of cytokines on MBP expression.
Main Results:
- Increased mRNA and protein expression of MBP was observed in the hippocampus and cerebellum of recovered mice.
- Immunohistochemistry revealed an increased MBP-staining signal in the brains of recovered mice.
- Electron microscopy showed an increased G-ratio in both the hippocampus and cerebellum, indicating altered myelination.
- In vitro studies suggested that proinflammatory cytokines may induce MBP upregulation.
Conclusions:
- Neonatal influenza infection alters brain myelination properties in mice.
- Increased MBP expression may represent a compensatory mechanism related to hypomyelination following influenza infection.
- These myelination changes could underlie the observed neural dysfunction in influenza-recovered mice.
Abstract:
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.
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