Maternal-fetal type I interferon signaling drives TREM2 dysregulation and synaptic dysfunction in neurodevelopmental disorders.

Maternal type I interferon signaling causes TREM2 dysregulation and synaptic dysfunction in offspring, contributing to neurodevelopmental disorders.

• Why it matters: Understanding how maternal infections influence offspring brain development is crucial, as these interactions increase the risk of neurodevelopmental disorders like schizophrenia. Addressing this gap can lead to targeted interventions to prevent or mitigate such conditions.
• What they did: Using a maternal immune activation model with poly(I:C), researchers examined hippocampal changes in juvenile offspring, focusing on microglial TREM2 expression, synaptic homeostasis, and interferon responses, including analysis of human postmortem tissues.
• The result: Blocking maternal IFN-I signaling restored TREM2 function and normalized synaptic and microglial signatures, indicating that targeting IFN-I pathways during pregnancy could prevent neurodevelopmental impairments.