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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
The role of microglia in early neurodevelopment and the effects of maternal immune activation
L J M Mastenbroek1, S M Kooistra2, B J L Eggen2
1Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Abstract:
Activation of the maternal immune system during gestation has been associated with an increased risk for neurodevelopmental disorders in the offspring, particularly schizophrenia and autism spectrum disorder. Microglia, the tissue-resident macrophages of the central nervous system, are implicated as potential mediators of this increased risk. Early in development, microglia start populating the embryonic central nervous system and in addition to their traditional role as immune responders under homeostatic conditions, microglia are also intricately involved in various early neurodevelopmental processes. The timing of immune activation may interfere with microglia functioning during early neurodevelopment, potentially leading to long-term consequences in postnatal life. In this review we will discuss the involvement of microglia in brain development during the prenatal and early postnatal stages of life, while also examining the effects of maternal immune activation on microglia and neurodevelopmental processes. Additionally, we discuss recent single cell RNA-sequencing studies focusing on microglia during prenatal development, and hypothesize how early life microglial priming, potentially through epigenetic reprogramming, may be related to neurodevelopmental disorders.
Insights
Maternal immune activation during pregnancy may increase neurodevelopmental disorder risk in offspring. Microglia (brain immune cells) play a key role, with early life priming potentially linked to these disorders.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Maternal immune activation during pregnancy is linked to offspring neurodevelopmental disorders like schizophrenia and autism spectrum disorder.
- Microglia, the brain's resident immune cells, are crucial for early neurodevelopment and may mediate this risk.
- The timing of immune activation can disrupt microglia function, causing lasting effects.
Purpose of the Study:
- To review the role of microglia in prenatal and early postnatal brain development.
- To examine the impact of maternal immune activation on microglia and neurodevelopment.
- To explore the connection between early microglial priming and neurodevelopmental disorders.
Main Methods:
- Review of existing literature on maternal immune activation and neurodevelopment.
- Analysis of microglia's role in embryonic and early postnatal brain development.
- Discussion of single-cell RNA-sequencing data on prenatal microglia.
Main Results:
- Microglia are involved in critical neurodevelopmental processes beyond immune response.
- Maternal immune activation can alter microglia function during sensitive developmental windows.
- Early microglial priming, potentially via epigenetic changes, is hypothesized to contribute to neurodevelopmental disorders.
Conclusions:
- Microglia are central players in how maternal immune activation affects offspring neurodevelopment.
- Understanding microglia's early life programming is key to addressing neurodevelopmental disorder risks.
- Further research into microglial epigenetic reprogramming may reveal therapeutic targets.
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