DDT and titanium dioxide nanoparticle coexposure induced neurobehavioral deficits in zebrafish

Both dichlorodiphenyltrichloroethane (DDT) and titanium dioxide nanoparticle (TiO₂ NP) have worldwide-scale commercial applications, resulting in their co-pollution in the ecosystems and posing combined health risks. However, there is a lack of toxicity studies for the interactions of DDT and TiO₂ NP in the environmental relevant concentrations. In this study, we characterized the coexposures using a zebrafish waterborne exposure approach and evaluated the neurotoxicity response of the treated embryos or adults. Our results showed that DDT/TiO₂ NP coexposure enhanced the DDT accumulation in vivo and increased the larval locomotor. The chronic DDT/TiO₂ NP coexposure did not affect the overall survival rate, sex ratio and growth. However, DDT/TiO₂ NP coexposure severely affected the adult locomotor activity, social contact, shoaling and aggressive behaviors compared to single treatment groups or controls. These adult behavioral deficits were accompanied by changes in neurotransmitter acetylcholine (ACH) level in the brain and muscle tissues, as well as neural development genes expression activation of growth-associated protein 43 (gap43) and synaptic vesicle glycoprotein 2 (sv2) in the brain. The significantly increased ACH level and the activated neural genes expression in the DDT/TiO₂ NP co-exposed fish may account for the observed hyperactivity and social deficits.