The Effect Of Apoptosis Induced By Arsenic On Bcl-2and Bax Gene Expressions In Hippocampus Of Mice

Objective: The present study was to investigate the apoptotic effect induced byarsenic on Bcl-2and Bax gene expression in hippocampus of mice, which could providea basis to clarify the neurotoxicity mechanism and prevention of arsenic neurotoxicity.Methods: SPF mice of either sex were randomly divided into four groups (ten foreach): the control group、1ppm As2O3、2ppm As2O3、4ppm As2O3. Mice were exposedto sodium arsenite through drinking water for60days. After that8mice were chosenfrom each group and removed the hippocampus on ice rapidly to analyze the expressionof Bcl-2and Bax by PCR and Western blot method. Another2mice from each groupwere deeply anesthetized by ether and perfused with4%paraformaldehyde to assess byTUNEL assay and transmission electron microscopy.Results: TUNEL labeling demonstrates the emergence of DNA fragmentation inthe CA1region and other region of hippocampus following4ppm arsenicadministration, and transmission electron microscopy of4ppm-arsenic treated miceneuron also showing typical features of a cell, while the DNA fragmentation from thecontrol is negligible. Real time PCR results showed that Bcl-2was down-regulated inhippocampus tissue of mice exposed to As, and the expression of gen Bax wasincreased comparing to the control group. Furthermore, the quantity of Bcl-2band inthe group exposed to4ppm As2O3decreased compared to the control group, and,conversely the quantity of Bax band significantly increased, agreeing well with the PCRresult.Conclusion: Subchronic arsenic exposure induced hippocampal neuronalapoptosis of mice, lowered Bcl-2gene and protein expression and up-regulated Baxgene and protein expression. The hippocampal neuronal apoptosis in mice exposed to arsenic may relate with the Bcl-2down-regulation and Bax up-regulation.