Increased RNA editing in maternal immune activation model of neurodevelopmental disease

Nat Commun. 2020 Oct 16;11(1):5236. doi: 10.1038/s41467-020-19048-6.

Abstract

The etiology of major neurodevelopmental disorders such as schizophrenia and autism is unclear, with evidence supporting a combination of genetic factors and environmental insults, including viral infection during pregnancy. Here we utilized a mouse model of maternal immune activation (MIA) with the viral mimic PolyI:C infection during early gestation. We investigated the transcriptional changes in the brains of mouse fetuses following MIA during the prenatal period, and evaluated the behavioral and biochemical changes in the adult brain. The results reveal an increase in RNA editing levels and dysregulation in brain development-related gene pathways in the fetal brains of MIA mice. These MIA-induced brain editing changes are not observed in adulthood, although MIA-induced behavioral deficits are observed. Taken together, our findings suggest that MIA induces transient dysregulation of RNA editing at a critical time in brain development.

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / growth & development
  • Brain / immunology
  • Brain / metabolism
  • Disease Models, Animal
  • Female
  • Immunity, Maternally-Acquired
  • Mice
  • Mice, Inbred C57BL
  • Neurodevelopmental Disorders / etiology*
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / immunology
  • Neurodevelopmental Disorders / psychology
  • Poly I-C / adverse effects
  • Poly I-C / immunology
  • Pregnancy / immunology*
  • Pregnancy Complications / etiology
  • Pregnancy Complications / genetics
  • Pregnancy Complications / immunology*
  • Prenatal Exposure Delayed Effects / genetics*
  • Prenatal Exposure Delayed Effects / immunology
  • Prenatal Exposure Delayed Effects / psychology
  • RNA Editing*

Substances

  • Poly I-C