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.

December 7, 2022


CGM Primary Investigator

Rakesh Karmacharya