Fetal brain response to maternal inflammation requires microglia

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• Maternal inflammation impacts fetal brain development and increases neuropsychiatric disorder risk in offspring.
• The specific brain cells mediating fetal responses to maternal inflammation are not well understood.

Purpose of the Study:

• To identify the cell types involved in the fetal brain's response to maternal inflammation.
• To investigate the role of microglia in mediating the effects of maternal immune activation (MIA) on fetal brain development.

Main Methods:

• Utilized a rodent model of maternal immune activation (MIA) by injecting pregnant mice with polyinosinic:polycytidylic acid.
• Analyzed transcriptional changes in fetal microglia and other cortical cells.
• Investigated the effects of microglia-specific genetic deletion on MIA-induced gene expression changes.

Main Results:

• Microglia express high levels of pathogen and cytokine receptors during embryonic development.
• MIA induced persistent, long-lasting transcriptional alterations in fetal microglia.
• MIA caused widespread gene expression changes in neuronal and non-neuronal cells, which were dependent on the presence of microglia.

Conclusions:

• Microglia play a critical and durable role in the fetal brain's response to maternal inflammation.
• Microglia are essential mediators of MIA-induced transcriptional changes in other cortical cell types.
• Microglia represent a promising therapeutic target for mitigating adverse effects of maternal inflammation on fetal brain development.