Effect of arsenic exposure on learning and memory in rat models and its underlying mechanisms

Objective To explore the effects of arsenic exposure on learning and memory and its potential mechanism in rats. Methods Water-based arsenic-exposed rat models were established on 4-10 postnatal days.The experimental animals were divided into 4 groups (10-12 cases in each group): the control group, the 15 μg/L As2O3 water group, the 30 μg/L As2O3 water group, and the 45 μg/L As2O3 water group.Cognitive functions were examined with the Morris water maze, exploratory behavior was detected by the exploratory behavior test.The hippocampus of pups from each experimental group was sectioned at various time points after arsenic exposure.The morphologies and neurogenesis of the neurons in the hippocampus CA1-CA3 region and dentate gyrus (DG) were observed by hematoxylin-eosin staining, Nissl staining, and doublecortin (DCX) immunostaining at different time points after arsenic exposure. Results Compared with the normal control group, the escape latency of the rats in the arsenic-exposed group was prolonged.The average escape latency of the rats in the normal control group, 15 μg/L As2O3 group, 30 μg/L As2O3 group and 45 μg/L As2O3 group were (17.00±9.53) s, (35.89±19.81) s, (26.60±18.84) s, and (33.79±18.08) s, respectively, and the difference among 4 groups was statistically significant (F=3.591, P<0.05), and the residence time in the original target quadrant was shortened, respectively, (38.93±8.33) s, (36.03±16.25) s, (29.85±9.27) s, and (29.84±10.16) s, respectively, and there was no significant difference among 4 groups (F=1.681, P=0.187). HE staining and Nissl staining showed that pathological changes such as edema, degeneration and necrosis were observed in the hippocampal CA1 area and CA2 area as well as dentate gyrus cells in rats exposed to arsenic in the acute phase.The higher the concentration of arsenic exposure, the more obvious the cell structure disorder was.However, 5 weeks after exposure, the pathological changes in hippocampal neurons in the arsenic-exposed group gradually returned to normal.Immunohistochemistry showed that the expressions of DCX in the CA1, CA2 and dentate gyrus of rats exposed to arsenic decreased significantly 24 h after arsenic exposure, especially in the 45 μg/L group.Five weeks after arsenic exposure, there was no expression in the hippocampal CA1-CA3 area, and there was still a small amount of expression in the dentate gyrus. Conclusions Postnatal low-concentration arsenic exposure may impair learning and abnormal germination of neurons in the hippocampal dentate gyrus may be the underlying mechanism. Key words: Arsenic exposure; Learning and memory; Hippocampus; Mechanism