Interferon hypersensitivity in the brain of a Down syndrome preclinical model

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21). People with DS have altered neuroinflammation, including abnormal microglial morphology and elevated cytokines. The peripheral immune system is also different in DS, including an over‐activated interferon response likely due to four genes encoding interferon receptors being located on Hsa21. How this affects neuroinflammation is unknown. The “ex vivo” model system of organotypic brain slice cultures (OBSCs) derived from mouse brain can be used to model neuroinflammation. We created OBSCs from a DS preclinical mouse model containing three copies of the interferon receptor genes, and treated them with interferon‐β to investigate if this model had a hyper‐sensitive interferon response in the brain.