Neurobehavioral Toxic Effects and Mechanisms of 2-Aminobenzothiazole Exposure on Zebrafish

Abstract

2-Aminobenzothiazole (NTH), a benzothiazole derivative, exhibits potent biochemical activities and plays a significant role in modern industry. Widespread and intensive utilization of NTH has led to its detection in aquatic environments, encompassing both groundwater and surface water. Despite its wide usage, the effect of NTH on developmental neurotoxicity in aquatic organisms remains uncharted. Therefore, the aim of this investigation was to create exposure models for short- and long-term studies in order to analyse the neurobehavioural toxic impact of NTH (0, 50, 500, and 5000 μg/L) on zebrafish, which includes motor function, anxiety, and memory performance, as well as to examine the mechanism of neurotoxicity. The results revealed a significant suppression of initial embryonic mobility by NTH. However, during short-term exposure experiments, it did not significantly impact the developmental neurobehavioral functions of zebrafish. In addition, significant effects on zebrafish were observed after long-term exposure to 50 and 500 μg/L NTH, mainly impacting locomotion, social behaviour, anxiety, and cognitive functions. Moreover, NTH caused oxidative damage in adult zebrafish brain tissue, which was accompanied by abnormal expression of oxidative damage-related genes. Furthermore, the Real-Time PCR results indicated a significant suppression of genes related to exposure to NTH, specifically those in the GABA synthesis pathway (gabrg2, gad2, gad1b, and abat) and the 5-HT synthesis pathway (tph2, tph1b, pet1, and htr1aa). Taken together, this study demonstrates for the first time that chronic exposure to NTH decreases the expression of genes associated with the zebrafish baramine synthesis pathway and the 5-hydroxytryptamine synthesis pathway. This suppression is accompanied by oxidative damage, ultimately resulting in neurobehavioural changes related to motor ability, anxiety, and memory performance.

Keywords: 2-Aminobenzothiazole, zebrafish, short- and long-term exposure, Neurotoxicity