'Environmental standard limit concentration' arsenic exposure is associated with anxiety, depression, and autism-like changes in early-life stage zebrafish

Arsenic is a worldwide environmental pollutant that can impair human health. Previous studies have identified mental disorders induced by arsenic, but the environmental exposure concentrations in the early life stages associated with these disorders are poorly understood. In the present study, early-life stage zebrafish were used to explore the effects on mental disorders under 'environmental standard limit concentrations' arsenic exposures of 5, 10, 50, 150, and 500μg/L. The results showed that arsenic exposure at these concentrations changed the locomotor behavior in larval zebrafish and was further associated with anxiety, depression, and autism-like behavior in both larval and juvenile zebrafish. Changes were noted at benchmark dose limit (BMDL) concentrations as low as 0.81μg/L. Transcriptomics showed that immediate early genes (IEGs) fosab, egr1, egr2a, ier2b, egr3, and jund were decreased after arsenic exposure in larval and juvenile zebrafish. Nervous system impairment and anxiety, depression, and autism-like behaviors in early-life stage zebrafish at 'environmental standard limit concentrations' may be attributed to the downregulation of IEGs. These findings in zebrafish provided new experimental support for an arsenic toxicity threshold for mental disorders, and they suggest that low levels of environmental chemicals may be causative developmental factors for mental disorders. Environmental Implication Over the past decades, many studies have focused on arsenic-induced cancer; however, little is known about arsenic-induced mental disorders. In the present study, early-life stage zebrafish were used to explore the neurobehavior changes and potential molecular mechanisms under 'environmental standard limit concentrations' arsenic exposures. The results showed that some neurobehavior changes occurred at exposure levels using the Bayesian Benchmark Dose (BBMD) method. The results of this study provided experimental support for revised arsenic safety limits for aquatic environments, and they suggest that exposures to arsenic at low concentrations may be factors affecting the mental health.