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Updated: Aug 4, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Maternal immune activation alters fetal and neonatal microglia phenotype and disrupts neurogenesis in mice
Marco Loayza1, Shuying Lin2, Kathleen Carter1
1Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Background:
Activation of microglia, increase in cortical neuron density, and reduction in GABAergic interneurons are some of the key findings in postmortem autism spectrum disorders (ASD) subjects. The aim of this study was to investigate how maternal immune activation (MIA) programs microglial phenotypes and abnormal neurogenesis in offspring mice.
Methods:
MIA was induced by injection of lipopolysaccharide (LPS, i.p.) to pregnant mice at embryonic (E) day 12.5. Microglial phenotypes and neurogenesis were investigated between E15.5 to postnatal (P) day 21 by immunohistochemistry, flow cytometry, and cytokine array.
Results:
MIA led to a robust increase in fetal and neonatal microglia in neurogenic regions. Homeostatic E15.5 and P4 microglia are heterogeneous, consisting of M1 (CD86+/CD206-) and mixed M1/M2 (CD86+/CD206+)-like subpopulations. MIA significantly reduced M1 but increased mixed M1/M2 microglia, which was associated with upregulation of numerous cytokines with pleotropic property. MIA resulted in a robust increase in Ki67+/Nestin+ and Tbr2+ neural progenitor cells in the subventricular zone (SVZ) of newborn mice. At juvenile stage, a male-specific reduction of Parvalbumin+ but increase in Reelin+ interneurons in the medial prefrontal cortex was found in MIA offspring mice.
Conclusions:
MIA programs microglia towards a pleotropic phenotype that may drive excessive neurogenesis in ASD patients.
Impact:
Maternal immune activation (MIA) alters microglial phenotypes in the brain of fetal and neonatal mouse offspring. MIA leads to excessive proliferation and overproduction of neural progenitors in the subventricular zone (SVZ). MIA reduces parvalbumin+ while increases Reelin+ interneurons in the prefrontal cortex. Our study sheds light on neurobiological mechanisms of abnormal neurogenesis in certain neurodevelopmental disorders, such as autism spectrum disorder (ASD).
Insights
Maternal immune activation in mice programs microglia and increases neural progenitor cells, potentially contributing to neurodevelopmental disorders like autism spectrum disorder (ASD). This research highlights altered microglial phenotypes and abnormal neurogenesis in offspring.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Autism spectrum disorder (ASD) is associated with microglial activation, increased cortical neuron density, and reduced GABAergic interneurons.
- Understanding the impact of maternal immune activation (MIA) on offspring neurodevelopment is crucial for identifying potential mechanisms underlying ASD.
Purpose of the Study:
- To investigate how maternal immune activation (MIA) influences microglial phenotypes and neurogenesis in mouse offspring.
- To explore the neurobiological underpinnings of abnormal neurogenesis in the context of MIA.
Main Methods:
- Maternal immune activation (MIA) induced by lipopolysaccharide (LPS) injection in pregnant mice.
- Analysis of microglial phenotypes and neurogenesis from embryonic to postnatal stages using immunohistochemistry, flow cytometry, and cytokine arrays.
- Investigation of neural progenitor cells and interneuron populations in specific brain regions.
Main Results:
- MIA increased fetal and neonatal microglia, shifting phenotypes towards a mixed M1/M2-like state and upregulating cytokines.
- A significant increase in neural progenitor cells was observed in the subventricular zone (SVZ) of MIA offspring.
- Male MIA offspring exhibited reduced Parvalbumin+ and increased Reelin+ interneurons in the medial prefrontal cortex.
Conclusions:
- Maternal immune activation reprograms microglia towards a pleotropic phenotype.
- This altered microglial state may contribute to excessive neurogenesis observed in some autism spectrum disorder (ASD) cases.
- The study provides insights into the neurobiological mechanisms of abnormal neurogenesis in neurodevelopmental disorders.
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