期刊
CELLS
卷 11, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/cells11040738
关键词
beta-lactoglobulin; blood-brain barrier; cow's milk allergy; demyelination; histamine; IgE; IgG; neuroinflammation; proteases; astrocyte
类别
Through studies in a mouse model, we found that MC numbers increased in the brains of sensitized mice. Activation of beta-lactoglobulin resulted in changes in mobility and behavior, as well as neuroinflammatory responses in the brain.
Mast cells (MCs) are the major effector cells of allergic responses and reside throughout the body, including in the brain and meninges. Previously, we showed in a mouse model of subclinical cow's milk allergy that brain MC numbers were elevated in sensitized mice. However, the neurophysiological consequences of intracranial MC accumulation and activation are unclear. We hypothesized that centrally recruited MCs in sensitized mice could be activated by the allergen via the IgE/Fc epsilon RI mechanism and increase the blood-brain barrier (BBB) permeability to promote neuroinflammation. Furthermore, we suspected that repeated allergen exposure could sustain MC activation. To investigate our hypothesis, we sensitized C57BL6/J mice to a bovine whey allergen, beta-lactoglobulin (BLG), and subsequently placed them on a whey-containing diet for two weeks. MC activity and associated changes in the brain were examined. BLG-sensitized mice showed mobility changes and depression-like behavior with significantly increased MC numbers and histamine levels in select brain regions. IgG extravasation and perivascular astrogliosis were also evident. Importantly, myelin staining revealed cortical demyelination in the BLG-sensitized mice, suggesting a potential neural substrate for their behavioral changes. Our findings support the ability of brain MCs to release histamine and other mediators to increase BBB permeability and facilitate neuroinflammatory responses in the brain.
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