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

Germundson-Hermanson, D;


▪ 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.