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镉暴露损害雄性 C57BL/6 小鼠的认知和嗅觉记忆。

Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice.

机构信息

Toxicology Program, Department of Environmental and Occupational Health Sciences.

Department of Pharmacology, University of Washington, Seattle, Washington 98195.

出版信息

Toxicol Sci. 2018 Jan 1;161(1):87-102. doi: 10.1093/toxsci/kfx202.

Abstract

Cadmium (Cd) is a heavy metal of high interest to the superfund initiative. Recent epidemiology studies have suggested a possible association between Cd exposure and cognitive as well as olfactory impairments in humans. However, studies in animal models are needed to establish a direct causal relationship between Cd exposure and impairments in cognition and olfaction. This study aims to investigate the toxic effect of Cd on cognition and olfactory function in mice. One group of 8-week-old C57BL/6 male mice was exposed to 3 mg/l Cd (in the form of CdCl2) through drinking water for 20 weeks for behavior tests and final blood Cd concentration analysis. The behavior tests were conducted before, during, and after Cd exposure to analyze the effects of Cd on cognition and olfactory function. Upon completion of behavior tests, blood was collected to measure final blood Cd concentration. Two additional groups of mice were similarly exposed to Cd for 5 or 13 weeks for peak blood Cd concentration measurement. The peak blood Cd concentration was 2.125-2.25 μg/l whereas the final blood Cd concentration was 0.18 μg/l. At this exposure level, Cd impaired hippocampus-dependent learning and memory in novel object location test, T-maze test, and contextual fear memory test. It also caused deficits in short-term olfactory memory and odor-cued olfactory learning and memory. Results in this study demonstrate a direct relationship between Cd exposure and cognitive as well as olfactory impairments in an animal model.

摘要

镉 (Cd) 是超级基金计划高度关注的重金属。最近的流行病学研究表明,人类接触镉与认知和嗅觉损伤之间可能存在关联。然而,需要在动物模型中进行研究,以建立镉暴露与认知和嗅觉损伤之间的直接因果关系。本研究旨在调查 Cd 对小鼠认知和嗅觉功能的毒性作用。一组 8 周龄雄性 C57BL/6 小鼠通过饮用水暴露于 3mg/l Cd(以 CdCl2 的形式)20 周,进行行为测试和最终血液 Cd 浓度分析。在进行行为测试之前、期间和之后进行行为测试,以分析 Cd 对认知和嗅觉功能的影响。完成行为测试后,采集血液以测量最终血液 Cd 浓度。另外两组小鼠以类似的方式暴露于 Cd 5 或 13 周,以测量血液 Cd 浓度峰值。血液 Cd 浓度峰值为 2.125-2.25μg/l,而最终血液 Cd 浓度为 0.18μg/l。在这种暴露水平下,Cd 损害了新物体位置测试、T 迷宫测试和情景恐惧记忆测试中的海马依赖性学习和记忆。它还导致短期嗅觉记忆和气味提示嗅觉学习和记忆缺陷。本研究的结果表明,在动物模型中,Cd 暴露与认知和嗅觉损伤之间存在直接关系。

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