Phthalates induce neurotoxicity affecting locomotor and thermotactic behaviors and AFD neurons through oxidative stress in Caenorhabditis elegans.

Abstract

BACKGROUND: Phthalate esters are ubiquitous environmental contaminants and numerous organisms are thus exposed to various levels of phthalates in their natural habitat. Considering the critical, but limited, research on human neurobehavioral outcomes in association with phthalates exposure, we used the nematode Caenorhabditis elegans as an in vivo model to evaluate phthalates-induced neurotoxicity and the possible associated mechanisms. PRINCIPAL FINDINGS: Exposure to phthalates (DEHP, DBP, and DIBP) at the examined concentrations induced behavioral defects, including changes in body bending, head thrashing, reversal frequency, and thermotaxis in C. elegans. Moreover, phthalates (DEHP, DBP, and DIBP) exposure caused toxicity, affecting the relative sizes of cell body fluorescent puncta, and relative intensities of cell bodies in AFD neurons. The mRNA levels of the majority of the genes (TTX-1, TAX-2, TAX-4, and CEH-14) that are required for the differentiation and function of AFD neurons were decreased upon DEHP exposure. Furthermore, phthalates (DEHP, DBP, and DIBP) exposure at the examined concentrations produced elevated intracellular reactive oxygen species (ROS) in C. elegans. Finally, pretreatment with the antioxidant ascorbic acid significantly lowered the intracellular ROS level, ameliorated the locomotor and thermotactic behavior defects, and protected the damage of AFD neurons by DEHP exposure. CONCLUSIONS: Our study suggests that oxidative stress plays a critical role in the phthalate esters-induced neurotoxic effects in C. elegans.