Unraveling the neurobehavioral effects of toxin-induced inflammation 3310

Abstract Description Inflammation impacts brain function and behavior, as evidenced by sickness behaviors induced by type 1 immunity. However, the effects of type 2 inflammation on behavior and brain are unexplored. We chose bacterial cholera toxin (CTx), a known type 2 mucosal adjuvant and major global health concern, to determine its acute effects on the central nervous system. We administered CTx (0.8 mg/kg) intragastrically to female BALB/c mice, perfused them, and immunostained their brains for FOS. Behavioral analysis using the open field test showed that 6h post-CTx, females developed anxiolytic-like behavior (more time spent in the center and less time in the corners compared to controls). This effect was not observed at 24h or in male mice. Surprisingly, female C57BL/6 displayed the opposite, anxiety-like behavior upon CTx. Moreover, ingestion of a plant toxin, aconitine, also induced anxiety-like behavior in female and male BALB/c mice. These data suggest that the CTx impact on behavior is sex- and strain-dependent and that toxins do not induce universal behavioral outputs. We also found that CTx activated the central amygdala, a key region in anxiety responses. Overall, our data shows that type 2 stimuli can be sensed by the brain and trigger specific behaviors. This work contributes to understanding how different inflammatory stimuli can uniquely affect brain function and behavior, informing future therapeutic approaches for inflammation-related neurological and behavioral disorders. Funding Sources Hypothesis Fund ($150k) PI: Esther Borges Florsheim 01/01/2024-05/31/2025 This funding source does not cover meetings and traveling expenses. Topic Categories Neuroimmunology (NEUR)