Susceptibility and resilience to maternal immune activation are associated with differential expression of endogenous retroviral elements

Brain Behav Immun. 2023 Jan;107:201-214. doi: 10.1016/j.bbi.2022.10.006. Epub 2022 Oct 12.

Abstract

Endogenous retroviruses (ERVs) are ancestorial retroviral elements that were integrated into the mammalian genome through germline infections and insertions during evolution. While increased ERV expression has been repeatedly implicated in psychiatric and neurodevelopmental disorders, recent evidence suggests that aberrant endogenous retroviral activity may contribute to biologically defined subgroups of psychotic disorders with persisting immunological dysfunctions. Here, we explored whether ERV expression is altered in a mouse model of maternal immune activation (MIA), a transdiagnostic environmental risk factor of psychiatric and neurodevelopmental disorders. MIA was induced by maternal administration of poly(I:C) on gestation day 12 in C57BL/6N mice. Murine ERV transcripts were quantified in the placentae and fetal brains shortly after poly(I:C)-induced MIA, as well as in adult offspring that were stratified according to their behavioral profiles. We found that MIA increased and reduced levels of class II ERVs and syncytins, respectively, in placentae and fetal brain tissue. We also revealed abnormal ERV expression in MIA-exposed offspring depending on whether they displayed overt behavioral anomalies or not. Taken together, our findings provide a proof of concept that an inflammatory stimulus, even when initiated in prenatal life, has the potential of altering ERV expression across fetal to adult stages of development. Moreover, our data highlight that susceptibility and resilience to MIA are associated with differential ERV expression, suggesting that early-life exposure to inflammatory factors may play a role in determining disease susceptibility by inducing persistent alterations in the expression of endogenous retroviral elements.

Keywords: Cytokines; Endogenous retroviruses; Inflammation; Maternal immune activation; Neurodevelopmental disorders; Resilience; Schizophrenia.

MeSH terms

  • Animals
  • Family*
  • Mammals
  • Mice
  • Mice, Inbred C57BL
  • Vitamins*

Substances

  • Vitamins