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.

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