Oxidative Stress as a Mechanistic Link Between Subclinical Food Allergy and Behavioral Alterations 2334366

Abstract Introduction Mood and cognitive alterations are often reported in individuals with subclinical food allergies who are tolerant of offending foods. Using a mouse model of subclinical cow’s milk allergy (CMA), we previously demonstrated that CMA mice exhibited anxiety-like and/or depression-like behavior and cognitive decline after allergen consumption. While the adverse effects of peripheral inflammation on brain function are increasingly recognized, how mood and cognition are affected remain unclear. Because CMA mice also showed impaired blood-brain barrier (BBB) and elevated systemic and brain histamine levels, which can disrupt cerebrovascular homeostasis and induce inflammatory responses, we examined whether chronic food allergen exposure would lead to oxidative stress and alter neuronal activities in the brain. Methods C57BL/6J male mice were orally sensitized to a bovine whey allergen, β-lactoglobulin (BLG; Bos d 5), or vehicle alone and then placed on a whey-free diet for five weeks, followed by exposure to a whey-containing diet for two weeks. After behavioral testing, brains were collected for immunohistochemical analyses for oxidative stress and neuronal activation using 4-hydroxynonenal (4HNE) and c-Fos staining, respectively. Results BLG-sensitized mice showed increased 4HNE staining and decreased c-Fos expression compared to naïve and sham mice. These changes occurred in brain regions involved in mood and cognition, including the dorsal raphe nucleus, lateral septal nucleus, hippocampus, thalamus, and inferior colliculus, indicating that allergen consumption induced lipid peroxidation and reduced neuronal activities in select brain regions in CMA mice. Conclusion Our results support our hypothesis that consumption of offending foods causes oxidative stress in the brain, providing a possible mechanism that links peripheral immune sensitization with altered brain function. Controlling oxidative stress may be a beneficial intervention for mitigating allergy-associated mood and cognitive disorders. Funding Source National Institute of Health grant number R01AI168563 Topic Categories Neuroimmunology (NEUR)