1. Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring
- Author
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Mirabella, Filippo, Desiato, Genni, Mancinelli, Sara, Fossati, Giuliana, Rasile, Marco, Morini, Raffaella, Markicevic, Marija, Grimm, Christina, Amegandjin, Clara, Termanini, Alberto, Peano, Clelia, Kunderfranco, Paolo, di Cristo, Graziella, Zerbi, Valerio, Menna, Elisabetta, Lodato, Simona, Matteoli, Michela, and Pozzi, Davide
- Abstract
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 elevation via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led to overall brain hyperconnectivity in offspring into adulthood. IL-6 activated synaptogenesis gene programs in glutamatergic neurons and required the transcription factor STAT3 and expression of the RGS4 gene. The STAT3-RGS4 pathway was also activated in neonatal brains during poly(I:C)-induced maternal immune activation, which mimics viral infection during pregnancy. These findings indicate that IL-6 elevation at early developmental stages is sufficient to exert a long-lasting effect on glutamatergic synaptogenesis and brain connectivity, providing a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders., Immunity, 54 (11)
- Published
- 2021