ArticleTranslational psychiatry2024
Differential effects of purified low molecular weight Poly(I:C) in the maternal immune activation model depend on the laboratory environment.
Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Maternal-fetal immune conflict contributes to male-specific impairments in a mouse model of neurodevelopmental disorders.Science advances · 2026Article
- Maternal immune activation in mice recapitulates features of attention-deficit/hyperactivity disorder (ADHD) in susceptible offspring.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Astroglial disinhibition of cortical circuits disrupts cognition via kynurenic acid in mice.Nature communications · 2026Article
- Maternal immune activation with high molecular weight poly (I:C) induces selective depressive-like phenotype in adult offspring.Translational psychiatry · 2026Article
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Abstract
The Poly (I:C) (polyriboinosinic-polyribocytidilic acid) paradigm of maternal immune activation (MIA) is most widely used as experimental model for the evaluation of the effects of gestational infection on the brain and behavior of the progeny. We have previously reported significant batch-to-batch variability in the effects of Poly (I:C), purchased from the same supplier (Sigma-Aldrich), on maternal and fetal immune responses and found these differences to be dependent on the relative amount of synthetic double-stranded RNA fragments in the high versus low molecular weight (LMW) range contained in the compound. We here resorted to Poly (I:C) purified for LMW dsRNA fragments to establish a MIA paradigm with increased reproducibility and enhanced standardization in an effort to refine the MIA paradigm and characterize its effect on offspring behavior. We found that the parallel application of LMW Poly (I:C) in two different MIA-experienced laboratories (Vienna and Zurich) yielded differential outcomes in terms of maternal immune responses and behavioral phenotypes in the offspring generation. In both experimental sites, administration of LMW Poly (I:C) induced a significant sickness response and cytokine induction in the pregnant dam and fetal brains, while the expected deficit in sociability as one main behavioral outcome parameter in the MIA progeny, was only present in the Zurich, but not the Vienna cohort. We conclude that although using Poly (I:C) purified for a defined molecular weight range reduces batch-to-batch variability, it does not make the MIA model more reliable and robust. The differential response in behavioral phenotypes of the MIA offspring between the two laboratories illustrates the highly complex interaction between prenatal and postnatal milieus - including the laboratory environment - that determine offspring phenotypic outcomes after MIA. Consequently, establishing a new MIA protocol or implementing the MIA model firstly under new or changed environmental conditions must include the assessment of offspring behavior to ensure solid and reproducible experimental outcomes.
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