The role of ROS/p38 MAPK/NLRP3 inflammasome cascade in arsenic-induced depression-/anxiety-like behaviors of mice

Arsenic pollution in groundwater remains a serious public health concern around the world. Recent years, arsenic-related neurological and psychiatric disorders have been reported increasingly. However, the exact mechanisms of it remains elusive. In this study, arsenic exposure through drinking water resulted in depression-/anxiety-like behaviors in mice accompanied by oxidative stress and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation in prefrontal cortex (PFC) and hippocampus, two main affected areas found in neurobehavioral disorders. Intervention by NAC, a ROS scavenger, diminished the social behavior impairments in mice as well as ROS generation and NLRP3 inflammasome activation. Further study revealed that it was p38 MAPK signaling pathway that mediated ROS-induced NLRP3 inflammasome activation. Overall, our findings suggested that ROS/p38 MAPK/NLRP3 inflammasome cascade was involved in arsenic-induced depression-/anxiety-disorders. Furthermore, NAC might be a potential therapeutic agent for arsenic-induced depression-/anxiety-disorders by inhibiting both ROS generation and ROS-induced NLRP3 inflammasome activation.