Cortical demyelination and depression-like behavior are associated with histaminergic dysregulation in a mouse model of peripheral inflammation

▪ Demyelinating diseases of the central nervous system are increasing in prevalence world-wide1,2 and manifest as motor, behavioral, and/or cognitive defects3 . The etiology and pathophysiology of demyelinating diseases remain unclear. ▪ We have previously observed cortical demyelination in our mouse model of non-anaphylactic cow’s milk allergy4 . The demyelination was associated with depression-like behaviors and region-specific increases in brain histamine and H3 receptor (H3R) levels4,5 . ❖ The brain’s central histaminergic system is tightly controlled and regulates many behaviors. Additionally, signaling through H3R plays a crucial role in oligodendrocyte differentiation, and thus, demyelination and remyelination6 . ▪ We hypothesized that excess histamine produced during the hypersensitivity response would influence behavior through dysregulation of the central histaminergic system, resulting in neuroinflammation and demyelination. ▪ To test our hypothesis, we treated our food allergy mouse model with thioperamide, an H3R antagonist, and examined whether blocking histaminergic signaling would ameliorate the aberrant behaviors and demyelination.https://commons.und.edu/bms-pp/1007/thumbnail.jp