Dimethyl phthalate exposure induces cognitive impairment through COX2-mediated microglial activation

Abstract

AIM We investigated the mechanism of action whereby exposure to dimethyl phthalate (DMP), an environmental pollutant, causes cognitive impairment. METHODS Network pharmacology was used to analyze the targets and regulatory networks associated with DMP-brain injury-cognitive impairment. The environmental intake of DMP was simulated by DMP exposure, and Morris water maze was adopted to examine cognitive impairment. The tissue levels of inflammatory cytokines were detected. Brain tissue damage was assayed by H&E and Nissl staining, and protein expression was identified by Western blotting. The effects of DMP were observed after separate application of siRNA-COX2 and celecoxib-COX2 inhibitors. In the in vitro experiment, the effects of DMP on microglia activation were investigated. RESULTS Network pharmacology revealed that PTGS2 (COX2) was significantly correlated with DMP, which could act through COX2. After exposure to DMP, mice showed significant brain injury and cognitive impairment, along with activation of microglia and upregulation of inflammatory cytokines. The application of siRNA-COX2 and celecoxib-COX2 could inhibit the effects of DMP and ameliorate the cognitive impairment in mice. The in vitro results showed that DMP could activate microglia and cause microglia activation and neuroinflammation. CONCLUSION DMP exposure can induce neuroinflammation through COX2-mediated activation of microglia, resulting in cognitive impairment. COX2 is an important target for DMP action.