Speaker
Description
Maternal infections during gestation cause perturbed neuroimmune interactions and increased risk of neurodevelopmental disorders in the offspring. Microglia, the immune surveillant of the brain, express Triggering Receptor Expressed on Myeloid Cell 2 (TREM2), which regulates synapse elimination and neuronal cell metabolism during development. Using a maternal immune activation model with polyriboinosinic-polyribocytidilic acid [Poly(I:C)], Trem2-/- mice, and anti-Type I Interferon receptor (αIFN-IR) treatment, we investigated how maternal infections reshape the hippocampal landscape of the newborn. Poly(I:C) exposure elevated Type I Interferon (IFN-I) in pregnant dams, disrupting neuronal transcriptional trajectories and synapse homeostasis in juvenile offspring. Poly(I:C) offspring microglia exhibited reduced TREM2 expression, suppressed IFN-I-responsive substate, and impaired phagocytosis. Downregulation of synaptic genes and microglial IFN-I-signature was Trem2-dependent, highlighting its regulatory role in neurodevelopmental pathologies. Blocking maternal IFN-I signaling restored synaptic defects and TREM2 function, suggesting that monitoring IFN-I responses during pregnancy may represent viable therapeutic approaches to mitigate neurodevelopmental dysfunction in newborn.
| Author(s) | Matteo Bizzotto (1)*, Shih Feng You (3,4), Elisa Faggiani (1), Raffaella Morini (1), Ricardo d'Oliveira Albanus (3,4,5), Matteo Tamborini (1), Ekaterina Aldyeva (4), Aasritha Nallapu (4), Claudio Ferrari (2), Antonella Borreca (1,6), Oscar Harari (3,4,5), Celeste M. Karch (3,4,5), Michela Matteoli (1,2,6), Fabia Filipello (1,3) |
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| Affiliation(s) | "(1) IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089 Milan, Italy (2) Humanitas University, Department of Biomedical Sciences, Via Levi Montalicini 4, Pieve Emanuele 20072 Milan, Italy (3) Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA (4) NeuroGenomics and Informatics, Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA (5) Hope Center for Neurological Disorders, Washington University School of Medicine in St. Louis, St. Louis, MO, USA (6) Institute of Neuroscience - National Research Council, 20139 Milan, Italy" |
