Postnatal low-concentration arsenic exposure induces autism-like behavior and affects frontal cortex neurogenesis in rats.

This study aimed to explore the effects of postnatal low-concentration arsenic exposure on learning, social skills and frontal cortex neurogenesis in rats. Water-based arsenic exposure rat models were established on postnatal days 4-10 (P4-P10). The experimental animals were divided into four groups: the control group, a 15 μg/L As2 O3 water group, a 30 μg/L As2 O3 water group, and a 45 μg/L As2 O3 water group. Cognitive function was examined with the Morris water maze, anxiety-like behavior with the open field test and light-dark box test, and social skills with a social interaction test. The frontal cortices of pups from each experimental group were sectioned at various time points after arsenic exposure. The morphologies and neurogenesis of the neurons in the frontal cortices were observed by hematoxylin-eosin staining, Nissl staining, and doublecortin (DCX) immunostaining. Significant positive correlations between arsenic concentration and deficits in learning and social skills were found, and the arsenic exposure groups showed significant increases in anxiety-like behavior compared with the control group (all Ps<0.05). Abnormal morphologic changes in the external granular layer and external pyramidal layer were positively correlated with the water arsenic concentration in the acute phase of arsenic exposure. However, at five weeks after arsenic exposure, the frontal cortex morphology was restored. Moreover, immunohistochemistry revealed that compared to the control group, the groups that were exposed to arsenic exhibited significantly higher levels of DCX expression in the external granular and external pyramidal layers (all Ps<0.001). Furthermore, the 30 μg/L and 45 μg/L arsenic exposure groups still showed some DCX expression at five weeks after exposure. In conclusion, postnatal low-concentration arsenic exposure impaired learning and social skills and increased anxiety-like behaviors, and abnormal frontal cortex neurogenesis may be the mechanism underlying these effects.