Food Allergy Induces Anxiety-like Behavior and Neuroimmune Dysregulation in the Prefrontal Cortex of Mice

Food allergy (FA) is associated with anxiety, but the underlying mechanisms remain incompletely understood. An ovalbumin (OVA)-induced FA model was established in female BALB/c mice to evaluate anxiety-like behavior and characterize molecular alterations in the prefrontal cortex (PFC). We assessed the FA model by anaphylactic scores, OVA-specific IgE and IgG1 levels, serum cytokines, and intestinal histology, and evaluated anxiety-like behavior using the open field test (OFT) and elevated plus maze (EPM). Mice with OVA-induced food allergy exhibited pronounced allergic responses and intestinal mucosal injury, together with reduced center-zone exploration in the OFT and reduced open-arm exploration in the EPM. In the PFC, inflammatory and chemotactic mediators were increased, accompanied by enlarged Iba1-positive microglial soma area. Bulk RNA sequencing identified 183 differentially expressed genes, including upregulated genes involved in immune and inflammatory responses and downregulated genes associated with neuronal activity and plasticity. Western blotting further showed an increased p-Akt (Ser473)/Akt ratio. These findings reveal that OVA-induced food allergy in female BALB/c mice is associated with neuroimmune dysregulation and broader transcriptional alterations in the PFC involving immune and inflammatory responses and processes related to neuronal activity and plasticity, and suggest that altered Akt-related signaling may provide a molecular link between these changes.