Impact of selenium on cerebellar injury and mRNA expression in offspring of rat exposed to methylmercury.

During the fetal development stage, the Central Nervous System (CNS) is particularly sensitive to methylmercury (MeHg). However, the mechanism underlying the antagonistic effect of selenium (Se) on MeHg toxicity is still not fully understood. In this study, female rat models with MeHg and Se co-exposure were developed. Pathological changes in the cerebellum and differential mRNA expression profiles in offspring rats were studied. In the MeHg-exposed group, a large number of Purkinje cells showed pathological changes and mitochondria were significantly swollen; co-exposure with Se significantly improved the structure and organization of the cerebellum. In total, 378 differentially expressed genes (DEGs) (including 284 up-regulated genes and 94 down-regulated genes) in the cerebellum of the MeHg-exposed group and 210 DEGs (including 84 up-regulated genes and 126 down-regulated genes) in the cerebellum of the MeHg+Se co-exposed group were identified. The genes involved in neurotransmitter synthesis and release and calcium ion balance in the cerebellum were significantly up-regulated in the MeHg-exposed group. These genes in the MeHg+Se co-exposed group were not changed or down-regulated. These findings demonstrate that the neurotoxicity caused by MeHg exposure is related to the up-regulation of multiple genes in the nerve signal transduction and calcium ion signal pathways, which are closely related to impairments in cell apoptosis and learning and memory. Supplementation with Se can mitigate the changes to related genes and protect neurons in the mammalian brain (especially the developing cerebellum) from MeHg toxicity. Se provides a potential intervention strategy for MeHg toxicity.