Distinct effects of interleukin-6 and interferon-γ on differentiating human cortical neurons
The Karmacharya lab interrogated neurodevelopmental effects of exposure to interleukin-6 (IL-6) and interferon-γ (IFN-γ) in differentiating human cortical neurons. Transcriptomic analyses showed IL-6 exposure affected genes regulating extracellular matrix, actin cytoskeleton and TGF-β signaling while IFN-γ exposure impacted genes regulating antigen processing, major histocompatibility complex and endoplasmic reticulum biology. IL-6 altered mitochondrial respiration in the differentiated neurons while IFN-γ induced reduction in dendritic spine density. Pretreatment with folic acid ameliorated IL-6 effects on mitochondrial respiration and IFN-γ effects on dendritic spine density. These findings suggest cellular processes that mediate maternal immune activation in developing brains and how folic acid mitigates such risk.