Recent studies suggest that copper exposure, even at very low levels, can produce significant toxic effects on the brains of mice. This study is aimed to explore the effects of low levels of copper on the hippocampal proteome of mice. Two-dimensional fluorescence difference gel electrophoresis was performed on hippocampal homogenate obtained from mice, which were given either drinking water only (control) or water supplemented with 0.13 ppm copper (copper-treated) for a period of 8 months beginning at an age of 3 months. A total of 9 differentially expressed proteins between copper-treated mice and control mice were identified. Protein functional analysis revealed that the altered proteins mainly involved energy metabolism-related proteins, synaptic proteins, molecular chaperones and cellular structural components. Among these differentially expressed proteins, serine racemase (SRR) and glial fibrillary acidic protein (GFAP) were significantly down-regulated and up-regulated, respectively, in the hippocampus of copper-treated mice compared with the control mice. SRR was shown to be involved in memory formation. The increased expression of GFAP, an astrocyte marker, indicated that long-term low levels of copper exposure caused activation of the inflammatory response, a process linked to spatial memory impairment. In agreement with the data from proteomic analysis, memory impairment was observed in copper-treated mice as measured by the Morris water maze test. In summary, this study has identified a number of abnormally expressed proteins in the hippocampus of copper-treated mice, and the identified protein, such as SRR, together with inflammatory responses, as evidenced by the increased expression of GFAP, could contribute to memory impairment resulting from copper exposure. Our findings provide insights for a better understanding of copper neurotoxicity at the protein level in response to low levels of copper exposure.

中文翻译：

---

长期暴露于低水平铜后小鼠海马的蛋白质组学分析。

最近的研究表明，即使铜的暴露量非常低，它也会对小鼠的大脑产生明显的毒性作用。这项研究旨在探讨低水平的铜对小鼠海马蛋白质组的影响。对从小鼠获得的海马匀浆进行二维荧光差异凝胶电泳，从3岁开始，给小鼠仅饮水（对照）或补充有0.13 ppm铜的水（铜处理），为期8个月几个月。在铜处理的小鼠和对照小鼠之间总共鉴定出9种差异表达的蛋白质。蛋白质功能分析表明，改变的蛋白质主要涉及能量代谢相关蛋白质，突触蛋白质，分子伴侣和细胞结构成分。在这些差异表达的蛋白质中，与对照小鼠相比，铜处理小鼠的海马中丝氨酸消旋酶（SRR）和神经胶质纤维酸性蛋白（GFAP）分别显着下调和上调。SRR被证明与记忆形成有关。星形胶质细胞标志物GFAP的表达增加，表明长期低水平的铜暴露引起炎症反应的激活，这一过程与空间记忆障碍有关。与来自蛋白质组学分析的数据一致，通过莫里斯水迷宫测试测量，在铜处理的小鼠中观察到记忆障碍。总而言之，这项研究已经确定了铜治疗小鼠海马中许多异常表达的蛋白质，以及鉴定出的蛋白质（例如SRR）以及炎症反应，GFAP表达增加证明，铜暴露可能会导致记忆障碍。我们的发现为更好地了解铜在低水平暴​​露于铜的神经毒性方面提供了见识。