Exposure to di (2-ethylhexyl) phthalate causes locomotor increase and anxiety-like behavior via induction of oxidative stress in brain

Abstract

Di (2-ethylhexyl) phthalate (DEHP) is the most prevalent exposure scenario in the daily life. A growing number of significant studies showed that DEHP could exhibit long-term adverse health effects for the human body, particularly in the liver, kidneys, heart and reproductive systems. However, the impact of oral intake of DEHP on nervous system is extremely limited. In the present study, the adult C57BL/6J male mice were intragastric administered with two dosages DEHP for 35 days. The behavioral parameters were assessed using the elevated plus maze and open-field test. The mRNA expression levels of neuropeptides and the oxidative stress-associated proteins were detected by qPCR and western blot severally. The histopathologic alterations of brain were also observed by H&E and Nissl staining. The results demonstrated that oral DEHP exposure could result in neurobehavioral impairments such as locomotor increase and anxiety-like behavior. Furthermore, the pathological damages were clearly observed in cerebral cortex and hippocampus, accompanied by a decrease in neuropeptides and an increase in oxidative stress, which were all positively correlated with the dose of DEHP. Together, these findings provide valuable clues into the DEHP-induced neurotoxicity.