Elevated prenatal IL-6 levels disrupt early patterns of hippocampal electrical activity and chloride homeostasis by targeting GABAergic signaling at perinatal stage
Abstract
Early patterns of neuronal electrical activity are fundamental for driving critical developmental processes, including neuronal maturation and synapse formation. While genetic programs are key in orchestrating these events, the influence of environmental stressors remains poorly defined. Maternal immune activation (MIA) during pregnancy induces a systemic cytokine surge that can profoundly impact fetal brain development, increasing the risk of psychiatric and neurodevelopmental disorders. Here, we show that maternal elevation of interleukin-6 (IL-6) – a key cytokine upregulated during MIA – perturbs early hippocampal electrical activity in male offspring during the first postnatal week, a critical window for circuit formation. By triggering a STAT3-dependent modulation of early GABAergic synaptic transmission, IL-6 disrupts chloride homeostasis, causing a premature shift in the developmental GABA polarity switch. Our findings reveal a direct link between maternal immune signaling and early GABA-driven network maturation, providing insights into how inflammatory events during pregnancy may predispose male offspring to neurodevelopmental disorders.
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BibTeX
@article{desiato2026elevated,
title = {{Elevated prenatal IL-6 levels disrupt early patterns of hippocampal electrical activity and chloride homeostasis by targeting GABAergic signaling at perinatal stage}},
author = {Genni Desiato and Edoardo Fraviga and Thomas Cassani and Riccardo Grassi and Martina Vitali and Francesca Fanuele and Filippo Mirabella and Clara A. Amegandjin and Federica Ruggeri and Marco Cremonesi and David Andruszewski and Andrea Contestabile and Laura Cancedda and Riccardo Fesce and Graziella Di Cristo and Ilgiz A. Mufazalov and Marinos Kallikourdis and Michela Matteoli and Sebastiano Bariselli and Davide Pozzi},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78479-9},
url = {https://www.nature.com/articles/s41467-026-78479-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Elevated prenatal IL-6 levels disrupt early patterns of hippocampal electrical activity and chloride homeostasis by targeting GABAergic signaling at perinatal stage
AU - Genni Desiato
AU - Edoardo Fraviga
AU - Thomas Cassani
AU - Riccardo Grassi
AU - Martina Vitali
AU - Francesca Fanuele
AU - Filippo Mirabella
AU - Clara A. Amegandjin
AU - Federica Ruggeri
AU - Marco Cremonesi
AU - David Andruszewski
AU - Andrea Contestabile
AU - Laura Cancedda
AU - Riccardo Fesce
AU - Graziella Di Cristo
AU - Ilgiz A. Mufazalov
AU - Marinos Kallikourdis
AU - Michela Matteoli
AU - Sebastiano Bariselli
AU - Davide Pozzi
PY - 2026
DA - 2026/10/15
JO - Nature Communications
DO - 10.1038/s41467-026-78479-9
UR - https://www.nature.com/articles/s41467-026-78479-9
AB - Early patterns of neuronal electrical activity are fundamental for driving critical developmental processes, including neuronal maturation and synapse formation. While genetic programs are key in orchestrating these events, the influence of environmental stressors remains poorly defined. Maternal immune activation (MIA) during pregnancy induces a systemic cytokine surge that can profoundly impact fetal brain development, increasing the risk of psychiatric and neurodevelopmental disorders. Here, we show that maternal elevation of interleukin-6 (IL-6) – a key cytokine upregulated during MIA – perturbs early hippocampal electrical activity in male offspring during the first postnatal week, a critical window for circuit formation. By triggering a STAT3-dependent modulation of early GABAergic synaptic transmission, IL-6 disrupts chloride homeostasis, causing a premature shift in the developmental GABA polarity switch. Our findings reveal a direct link between maternal immune signaling and early GABA-driven network maturation, providing insights into how inflammatory events during pregnancy may predispose male offspring to neurodevelopmental disorders.
SN - 2041-1723
ER -