3-Phenoxybenzoic Acid Induces Neuronal Pentraxin 2 to Upregulate Complement Activity and Promotes Microglia-Mediated Neuronal Synaptic Damage.

Abstract

3-Phenoxybenzoic acid (3-PBA) has been demonstrated to be associated with neurrotoxicity, however, the precise mechanism through which it exerts its neurotoxic effects remains to be fully elucidated. In this study, an investigation was conducted into the neuroimmunotoxicity of 3-PBA from an immunological perspective, with a combination of traditional toxicological methods and computer simulations being utilized in the research process. In vivo, 3-PBA has been shown to cause microstructural damage to early synapses in the mouse brain, which is widely accepted as the primary cause of cognitive dysfunction in mice. In vivo, it has been demonstrated that synaptic damage is induced by the upregulation of complement activity by neuronal pentraxin 2 (NP2), which in turn promotes microglia-mediated synaptic damage. Moreover, molecular docking simulations confirmed the interaction between 3-PBA and NP2. The present findings extend from a neurotoxicity perspective to 3-PBA-associated computer simulations, highlighting NP2 as a molecular initiating protein for 3-PBA-induced neurotoxicity. Additionally, the heightened complement activity downstream facilitated synaptic harm by microglia, causing a decrease in synaptic density and ensuing cognitive impairment. The outcomes of this study expand our knowledge of the neurotoxic nature of 3-PBA and supply hints and a theoretical foundation for evaluating its risks.