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Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic PolyI:C
Published on: March 25, 2016
Prenatal infection leads to ASD-like behavior and altered synaptic pruning in the mouse offspring
Lourdes Fernández de Cossío1, Andrea Guzmán1, Suzanne van der Veldt2
1Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Quebec, Canada.
Abstract:
Environmental challenges to the maternal immune system during pregnancy have been associated with an increase in the frequency of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) appearing in the offspring. Microglia, the brain's resident immune-cells, are now known to be critically involved in normal brain development, shaping connections between neurons by pruning superfluous synaptic spines. Our aim was to investigate whether maternal infection during critical stages of gestation compromises the role of microglia in sculpting neuronal circuits. Using a mouse model of maternal immune activation (MIA) induced by bacterial Lipopolysaccharide (LPS), we assayed the offspring's behavior during postnatal development. Additionally, we quantified spines within the offspring's brain and assessed alterations in some molecular signals involved in pruning. LPS-induced MIA led to behavioral changes relevant to ASD in the offspring in the absence of gross neurological problems. Prenatal LPS resulted in a significant increase in the number of spines in the granule cells of the dentate gyrus, as well as a reduction in hippocampal expression of the fractalkine microglial receptor (CX3CR1), involved in mediating the pruning process in the offspring. Interestingly, these changes were only noted in the male progeny of the LPS challenged dams. These results provide an early indicator that microglial function is altered in the brain of offspring from immune challenged mothers and that the effects in the brain appear to be specific along sex lines.
Insights
Maternal infection during pregnancy may impact offspring brain development and increase Autism Spectrum Disorder (ASD) risk. This study found prenatal immune activation altered male offspring
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Maternal immune challenges during pregnancy are linked to neurodevelopmental disorders, including Autism Spectrum Disorders (ASD).
- Microglia, the brain's immune cells, play a crucial role in synaptic pruning essential for normal brain development.
- The impact of maternal immune activation on microglial function and its consequences for offspring neurodevelopment require further investigation.
Purpose of the Study:
- To investigate if maternal infection during gestation affects microglial-mediated synaptic pruning in offspring.
- To examine the behavioral and neurobiological consequences of maternal immune activation (MIA) on offspring.
- To determine if observed effects are sex-specific.
Main Methods:
- Utilized a mouse model of MIA induced by bacterial Lipopolysaccharide (LPS) exposure during critical gestation periods.
- Assessed offspring behavior for ASD-relevant changes during postnatal development.
- Quantified synaptic spine density and analyzed molecular signals (CX3CR1) involved in microglial pruning in offspring brains.
Main Results:
- LPS-induced MIA resulted in ASD-relevant behavioral alterations in offspring without gross neurological deficits.
- Prenatal LPS exposure led to increased spine density in the dentate gyrus granule cells of offspring.
- A reduction in hippocampal fractalkine receptor (CX3CR1) expression was observed in male offspring, suggesting impaired microglial pruning.
- These neurobiological changes were exclusively observed in male offspring of LPS-challenged dams.
Conclusions:
- Maternal immune activation during pregnancy can alter microglial function in the developing brain.
- Prenatal immune challenges may disrupt synaptic pruning, contributing to neurodevelopmental alterations.
- The observed effects on brain development and microglial function are sex-specific, impacting male offspring more significantly.
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