Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.02.364356v1?rss=1 Authors: Mirabella, F., Desiato, G., Mancinelli, S., Fossati, G., Rasile, M., Morini, R., Markicevic, M., Grimm, C., amegandjin, C., Termanini, A., Peano, C., Kunderfranco, P., DiCristo, G., Zerbi, V., Lodato, S., Menna, E., Matteoli, M., Pozzi, D. Abstract: Early prenatal inflammatory conditions are thought to represent a risk factor for different neurodevelopmental disorders, with long-term consequences on adult brain connectivity. Here we show that a transient IL-6 elevation, occurring at vulnerable stages of early neurodevelopment, directly impacts brain developmental trajectories through the aberrant enhancement of glutamatergic synapses and overall brain hyper-connectivity. The IL6-mediated boost of excitatory synapse density results from the neuronautonomous, genomic effect of the transcription factor STAT3 and causally involves the activation of RGS4 gene as a candidate downstream target. The STAT3/RGS4 pathway is also activated in neonatal brains as a consequence of maternal immune activation protocols mimicking a viral infection during pregnancy. By demonstrating that prenatal IL-6 elevations result in aberrant synaptic and brain connectivity through the molecular players identified, we provide a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders. Copy rights belong to original authors. Visit the link for more info