Gene-expression changes in cerium chloride-induced injury of mouse hippocampus. Mus musculus

Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure. Overall design: In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated.

本研究结果显示，氯化铈（CeCl3）暴露可导致海马损伤、细胞凋亡、氧化应激以及空间识别记忆功能受损。此外，基因芯片（microarray）数据显示，在2 mg/kg体重氯化铈暴露的小鼠海马组织中，154个参与学习记忆、免疫炎症、信号转导、细胞凋亡及应激响应的基因表达发生显著改变。
铈在现代社会的诸多领域应用广泛，涵盖农业、工业与医药行业。已有研究证实，铈可进入生态环境，并通过食物链传递至人体，对包括动物脑组织在内的多个器官产生毒性作用。然而，氯化铈的神经毒性分子机制尚未完全阐明。
本研究中，实验小鼠连续90天暴露于0.5、1及2 mg/kg体重的氯化铈，随后对其学习记忆能力与海马组织基因表达谱进行了检测分析。
本研究结果再次显示，氯化铈暴露可引发海马损伤、细胞凋亡、氧化应激及空间识别记忆功能受损。此外，基因芯片数据显示，在2 mg/kg体重氯化铈暴露的小鼠海马组织中，154个与学习记忆、免疫炎症、信号转导、细胞凋亡及应激响应相关的基因表达出现显著变化。
具体而言，Axud1、Cdc37与Ube2v1的显著上调可诱发严重细胞凋亡；而Adcy8、Fos及Slc5a7的表达受到显著抑制，则会导致小鼠认知功能受损。因此，Axud1、Cdc37、Ube2v1、Adcy8、Fos及Slc5a7或可作为氯化铈暴露所致海马毒性的潜在生物标志物。
研究设计概述：本研究中，实验小鼠连续90天暴露于0.5、1及2 mg/kg体重的氯化铈，随后对其学习记忆能力与海马组织基因表达谱展开了分析。