Analysis of search strategies for evaluating low-dose heavy metal mixture induced cognitive deficits in rats: An early sensitive toxicological approach
Analysis of search strategies for evaluating low-dose heavy metal mixture induced cognitive deficits in rats: An early sensitive toxicological approach
复制标题
评估低剂量重金属混合物引起的大鼠认知缺陷的搜索策略分析：一种早期敏感的毒理学方法
DOI：
10.1016/j.ecoenv.2020.110900
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发表时间：
2020-10-01
影响因子：
6.8
通讯作者：
Fan, Guangqin
中科院分区：
文献类型：
--
作者：
Jia, Qiyue;Zhang, Yuanyuan;Fan, Guangqin
铅（Pb）、镉（Cd）和汞（Hg）等重金属是典型的神经毒性污染物，可引起认知功能障碍。在人体血液中可以同时检测到低水平的这些污染物。在我们以前的研究中，行为表现显着受损暴露于这些重金属混合物（MM）在低水平。然而，所涉及的认知功能方面还没有得到很好的理解。在这里，我们进一步分析了搜索策略，使用一种新的算法命名为莫里斯水迷宫无偏策略分类（MUST-C）。幼鼠在胚胎期和哺乳期同时暴露于低剂量的铅、镉和汞。MM暴露在低剂量，在一般人群中发现的那些类似，损害搜索策略，即使他们的潜伏期和路径长度没有受到影响，在莫里斯水迷宫任务。MM暴露的大鼠更喜欢使用更多的无方向重复策略和更少的目标定位策略比溶剂暴露的动物在剂量依赖性的方式。此外，硫代巴比妥酸染色和电子显微镜进一步显示，MM暴露诱导海马CA 1和CA 3区剂量依赖性搜索策略相关的位置细胞损伤。这些结果表明，使用次优搜索策略的基础上暴露于低剂量的MM大鼠的早期认知缺陷。目前的研究确定，搜索策略分析可能是一种新的敏感的评估方法，用于评估在神经行为毒性。
Heavy metals such as lead (Pb), cadmium (Cd), and mercury (Hg) are representative neurotoxicological contaminants that can evoke cognitive dysfunctions. Low levels of these contaminants can be detected simultaneously in the human blood. In our previous study, behavioral performances were markedly impaired by exposure to these heavy metal mixtures (MM) at low levels. However, the aspects of cognitive functions involved are not well understood. Here, we further analyzed search strategies using a new algorithm named Morris water maze-unbiased strategy classification (MUST-C). Rat pups were co-exposed to low doses of Pb, Cd, and Hg during the embryonic and lactation stage. MM exposure at low doses, similar to those found in the general population, impaired search strategies even though their latency and path length were not affected in the Morris water maze task. MM-exposed rats preferred to use more directionless repetition strategies and less target orientation strategies than did vehicle-exposed animals in a dose-dependent manner. In addition, thionine staining and electron microscopy further revealed that MM exposure induced dose-dependent search strategy related place cell injures in the hippocampal CA1 and CA3 regions. These results demonstrate that the use of suboptimal search strategies underlies the early cognitive deficits in rats exposed to low doses of MM. The current study determined that search strategy analysis might be a novel sensitive assessment method for evaluating in the neurobehavioral toxicity.