Cytokine changes associated with the maternal immune activation (MIA) model of autism: A penalized regression approach

PLoS One. 2020 Aug 6;15(8):e0231609. doi: 10.1371/journal.pone.0231609. eCollection 2020.

Abstract

Maternal immune activation (MIA) during pregnancy induces a cytokine storm that alters neurodevelopment and behavior in the progeny. In humans, MIA increases the odds of developing neuropsychiatric disorders such as autism spectrum disorder (ASD). In mice, MIA can be induced by injecting the viral mimic polyinosinic:polycytidylic acid (poly(I:C)) to pregnant dams. Although the murine model of MIA has been extensively studied, it is not clear whether MIA results in cytokine changes in the progeny at early postnatal stages. Further, the murine model of MIA suffers from a lack of reproducibility and high inter-individual variability. Multivariable (MV) statistical analysis is widely used in human studies to control for confounders and covariates such as sex, age and exposure to environmental factors. We therefore reasoned that animal studies in general and studies on the MIA model in particular could benefit from MV analyses to account for complex phenotype interactions and high inter-individual variability. Here, we used MV statistical analysis to identify cytokines associated with MIA after adjustment for covariates. Besides confirming the association between previously described variables and MIA, we identified new cytokines that could play a role in behavioural alterations in the progeny during the early postnatal period.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / chemically induced
  • Autistic Disorder / etiology*
  • Behavior, Animal / physiology
  • Cytokines / adverse effects
  • Cytokines / immunology*
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Multivariate Analysis
  • Poly I-C / pharmacology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / immunology*
  • Reproducibility of Results

Substances

  • Cytokines
  • Poly I-C

Grants and funding

LD and NG acknowledge the generous support of the Fondation de France under the 2018 Program “Autisme et neurodéveloppement” and the 2017 Program “Recherche fondamentale et clinique sur les maladies psychiatriques”, respectively. CP is greatly indebted to the Labex Signalife PhD program from the Université Côte d'Azur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.