1109-IFN-I & TREM2 Dysregulation in Neurodevelopment

This research explores how maternal immune activation (MIA), triggered by viral-like infections during pregnancy, disrupts the brain development of offspring and increases the risk of neurodevelopmental disorders. By utilizing mouse models, researchers identified that an elevation in maternal type I interferon (IFN-I) leads to the dysregulation of TREM2, a vital protein that governs how immune cells prune synapses. This process causes significant synaptic dysfunction and altered neuronal activity in the developing hippocampus, mirroring genetic signatures found in postmortem tissues of schizophrenic patients. The study demonstrates that TREM2 deficiency prevents certain MIA-induced pathologies, while blocking maternal IFN-I signaling can successfully restore healthy brain function. Ultimately, these findings suggest that monitoring immune responses during pregnancy could provide a therapeutic pathway for mitigating long-term cognitive and behavioral impairments in children.

References:

• Matteo Bizzotto. Maternal-fetal type I interferon signaling drives TREM2 dysregulation and synaptic dysfunction in neurodevelopmental disorders, Neuron, 2026