Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring

• DOI: 10.1016/j.immuni.2021.10.006
• Publication Date: 2021-11-09T16:52:58Z
• Authors: Filippo Mirabella; Genni Desiato; Sara Mancinelli; Giuliana Fossati; Marco Rasile; Raffaella Morini; Marija Markicevic; Christina Grimm; Clara Amegandjin; Alberto Termanini; Clelia Peano; Paolo Kunderfranco; Graziella di Cristo; Valerio Zerbi; Elisabetta Menna; Simona Lodato; Michela Matteoli; Davide Pozzi
• Keywords: Synaptogenesis

Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led overall brain hyperconnectivity offspring adulthood. activated synaptogenesis gene programs neurons required the transcription STAT3 expression of RGS4 gene. The STAT3-RGS4 pathway was also neonatal brains poly(I:C)-induced maternal immune activation, which mimics viral infection pregnancy. These findings indicate at early stages is sufficient exert long-lasting effect on connectivity, providing mechanistic framework association between events