Related Experiment Video
Updated: Jun 25, 2025
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
PolyI:C Maternal Immune Activation on E9.5 Causes the Deregulation of Microglia and the Complement System in Mice,
Shuxin Yan1, Le Wang1,2, James Nicholas Samsom1
1Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, Canada.
Abstract:
Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to experimental factors, which has led to complexity in previous reports of the MIA phenotype. We sought to characterize an MIA protocol throughout development to understand how prenatal immune insult alters the trajectory of important neurodevelopmental processes, including the microglial regulation of synaptic spines and complement signaling. We used polyinosinic:polycytidylic acid (polyI:C) to induce MIA on gestational day 9.5 in CD-1 mice, and measured their synaptic spine density, microglial synaptic pruning, and complement protein expression. We found reduced dendritic spine density in the somatosensory cortex starting at 3-weeks-of-age with requisite increases in microglial synaptic pruning and phagocytosis, suggesting spine density loss was caused by increased microglial synaptic pruning. Additionally, we showed dysregulation in complement protein expression persisting into adulthood. Our findings highlight disruptions in the prenatal environment leading to alterations in multiple dynamic processes through to postnatal development. This could potentially suggest developmental time points during which synaptic processes could be measured as risk factors or targeted with therapeutics for neurodevelopmental disorders.
Insights
Maternal immune activation in mice led to reduced synaptic connections and altered microglial activity, impacting neurodevelopment long-term. These findings suggest potential therapeutic targets for neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Maternal immune activation (MIA) is linked to neurodevelopmental disorders.
- Existing animal models for MIA are complex and sensitive to experimental variables.
- Understanding MIA's developmental impact is crucial for identifying therapeutic strategies.
Purpose of the Study:
- To characterize the long-term effects of a specific MIA protocol on neurodevelopmental processes.
- To investigate microglial regulation of synaptic spines and complement signaling following prenatal immune insult.
- To establish a reliable animal model for studying MIA-associated neurodevelopmental alterations.
Main Methods:
- Induced MIA in CD-1 mice using polyinosinic:polycytidylic acid (polyI:C) on gestational day 9.5.
- Assessed dendritic spine density, microglial synaptic pruning, and complement protein expression across developmental stages.
- Utilized quantitative analyses of synaptic structures and protein markers.
Main Results:
- Reduced dendritic spine density observed in the somatosensory cortex from 3 weeks of age onwards.
- Increased microglial synaptic pruning and phagocytosis correlated with spine density loss.
- Dysregulation of complement protein expression persisted into adulthood.
Conclusions:
- Prenatal immune activation significantly alters neurodevelopmental trajectories, affecting synaptic integrity and microglial function.
- Increased microglial pruning is a key mechanism underlying MIA-induced synaptic loss.
- Complement system dysregulation and synaptic alterations persist into adulthood, offering potential therapeutic targets for neurodevelopmental disorders.
More Related Videos
09:09Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using PolyI:C to Study Susceptibility and Resilience in Offspring
Published on: August 17, 2022
08:50A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020