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Updated: May 7, 2026
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
Do prenatal immune activation and maternal iron deficiency interact to affect neurodevelopment and early behavior in
Louise Harvey1, Patricia Boksa1
1Department of Psychiatry, McGill University, Douglas Mental Health University Institute, 6875 La Salle Blvd, Verdun, H4H 1R3 Quebec, Canada.
Insights
Maternal iron deficiency and prenatal infection (LPS) during pregnancy independently harm offspring neurodevelopment. Combined exposures showed additive effects on neurodevelopmental abnormalities in rats, suggesting distinct biological pathways.
Area of Science:
- Neuroscience
- Developmental Biology
- Maternal Health
Background:
- Prenatal infection and iron deficiency are common pregnancy complications.
- Both exposures are linked to altered offspring brain development and are risk factors for schizophrenia.
- The combined effects of these exposures on neurodevelopment have not been previously studied.
Purpose of the Study:
- To investigate the interactive effects of prenatal immune activation and maternal iron deficiency on offspring neurodevelopment and behavior.
- To establish a rat model simulating these dual maternal insults.
Main Methods:
- Pregnant rats received either iron-sufficient or iron-deficient diets and were exposed to lipopolysaccharide (LPS) or saline during gestation.
- Offspring neurodevelopment and behavior were assessed using various reflexes and activity tests.
- Biochemical markers of inflammation and iron levels were measured in dams and offspring.
Main Results:
- Maternal iron deficiency exacerbated the inflammatory response to LPS.
- Offspring exposed to both insults showed more neurodevelopmental abnormalities than those exposed to a single insult.
- Neurodevelopmental effects were additive, indicating independent mechanisms of action for infection and iron deficiency.
Conclusions:
- Prenatal infection and maternal iron deficiency act additively to negatively impact offspring neurodevelopment.
- The findings suggest distinct biological pathways mediate the neurodevelopmental consequences of these common pregnancy complications.
- This study provides a novel model for investigating the combined impact of infection and nutritional deficiencies during critical developmental periods.
Abstract:
Infection and iron deficiency are common during pregnancy and studies have described altered brain development in the offspring as a result of these individual maternal exposures. Both exposures have been identified as risk factors for schizophrenia yet they have never been modeled simultaneously. We developed a rat model of prenatal immune activation on a background of maternal iron deficiency to determine whether these factors interact to affect neurodevelopment and early behavior in offspring. Pregnant rats were placed on iron sufficient (IS) or iron deficient (ID) diets from E2 to P7, and administered LPS or saline on E15/16. Iron was reduced in liver, spleen, serum and placenta from ID dams by E15. LPS administration on E15 caused greater induction of serum interleukin-6 and tumor necrosis factor-α in ID dams compared to IS dams. Offspring (P0, P7) from ID dams had reduced iron in spleen, liver and brain compared to IS, which normalized by P21. Pups from ID dams showed differences in forelimb grasp and acoustic startle, whilst pups from LPS dams displayed differences in grip ability, geotaxis reflex, cliff avoidance and acoustic startle. Offspring from LPS dams displayed reduced locomotor activity at P7 and P60; offspring from ID dams showed no change. Our findings show effects of prenatal LPS and maternal iron deficiency were additive, such that offspring exposed to both insults displayed more neurodevelopmental abnormalities than offspring exposed to one alone. Yet surprisingly there was no interaction between factors, suggesting independent mechanisms of action.
