Maternal immune activation induces sustained changes in fetal microglia motility

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• Maternal infection or inflammation during pregnancy can lead to fetal brain development abnormalities.
• These abnormalities are linked to cognitive impairments and increased susceptibility to neurodevelopmental disorders such as schizophrenia and autism spectrum disorders.
• Maternal immune activation (MIA) and elevated cytokine levels are proposed mediators, but microglial responses, particularly process motility, remain unclear.

Purpose of the Study:

• To investigate the impact of MIA induced at different gestational ages on microglial properties.
• To examine alterations in microglial morphology and process motility following MIA.
• To determine if impaired microglial function contributes to behavioral deficits and cognitive disease risks.

Main Methods:

• MIA was induced in pregnant mice at two distinct gestational ages (E12 and mid-pregnancy).
• Microglial morphology, IL-6 expression, and process motility were assessed at embryonic (E18) and postnatal stages.
• Behavioral tests were conducted to evaluate cognitive deficits.

Main Results:

• MIA in mid-pregnancy increased embryonic IL-6 expression but did not significantly alter microglial morphology.
• MIA, especially when induced earlier (E12), caused lasting changes in microglial process motility patterns.
• These motility alterations were associated with observable behavioral deficits.

Conclusions:

• Microglial process motility is a sensitive indicator of MIA effects on the developing brain.
• Impaired microglial motility following MIA may be a key mechanism linking maternal immune status to neurodevelopmental and cognitive disorders.
• Targeting microglial function could offer therapeutic strategies for mitigating MIA-induced risks.