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Analysis of search strategies for evaluating low-dose heavy metal mixture induced cognitive deficits in rats: An early sensitive toxicological approach.
Ecotoxicology and Environmental Safety ( IF 6.8 ) Pub Date : 2020-06-24 , DOI: 10.1016/j.ecoenv.2020.110900
Qiyue Jia 1 , Yuanyuan Zhang 1 , Sisi Liu 1 , Zongguang Li 1 , Fankun Zhou 1 , Lijian Shao 1 , Chang Feng 1 , Guangqin Fan 1
Affiliation  

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.



中文翻译:

分析评估低剂量重金属混合物诱发大鼠认知功能障碍的搜索策略:一种早期敏感的毒理学方法。

铅(Pb),镉(Cd)和汞(Hg)等重金属是可引起认知功能障碍的代表性神经毒理学污染物。可以同时在人血中检测到少量这些污染物。在我们之前的研究中,暴露于低浓度的这些重金属混合物(MM)会明显损害行为表现。然而,所涉及的认知功能的各个方面尚不十分清楚。在这里,我们使用名为Morris水迷宫无偏策略分类(MUST-C)的新算法进一步分析了搜索策略。在幼鼠的胚胎期和哺乳期,将其幼鼠共暴露于低剂量的Pb,Cd和Hg。低剂量的MM暴露,与一般人群中的剂量相似,即使在Morris水迷宫任务中不影响其潜伏期和路径长度,搜索策略也会受到影响。与媒介物暴露的动物相比,与媒介物暴露的动物相比,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靶标定向策略。此外,硫氨酸染色和电子显微镜进一步揭示,MM暴露诱导剂量依赖性搜索策略与海马CA1和CA3区的位置细胞损伤有关。这些结果表明,次优搜索策略的使​​用是暴露于低剂量MM大鼠的早期认知缺陷的基础。当前的研究确定搜索策略分析可能是一种新的敏感评估方法,用于评估神经行为毒性。与媒介物暴露的动物相比,与媒介物暴露的动物相比,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靶标定向策略。此外,硫氨酸染色和电子显微镜进一步显示,MM暴露诱导剂量依赖性搜索策略与海马CA1和CA3区的位置细胞损伤有关。这些结果表明,次最佳搜索策略的使​​用是暴露于低剂量MM大鼠的早期认知缺陷的基础。当前的研究确定搜索策略分析可能是一种新的敏感评估方法,用于评估神经行为毒性。与媒介物暴露的动物相比,与媒介物暴露的动物相比,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靶标定向策略。此外,硫氨酸染色和电子显微镜进一步揭示,MM暴露诱导剂量依赖性搜索策略与海马CA1和CA3区的位置细胞损伤有关。这些结果表明,次优搜索策略的使​​用是暴露于低剂量MM大鼠的早期认知缺陷的基础。当前的研究确定搜索策略分析可能是一种新的敏感评估方法,用于评估神经行为毒性。亚硫氨酸染色和电子显微镜进一步显示,MM暴露诱导的剂量依赖性搜索策略与海马CA1和CA3区的位置细胞损伤有关。这些结果表明,次优搜索策略的使​​用是暴露于低剂量MM大鼠的早期认知缺陷的基础。当前的研究确定搜索策略分析可能是一种新的敏感评估方法,用于评估神经行为毒性。亚硫氨酸染色和电子显微镜进一步显示,MM暴露诱导的剂量依赖性搜索策略与海马CA1和CA3区的位置细胞损伤有关。这些结果表明,次优搜索策略的使​​用是暴露于低剂量MM大鼠的早期认知缺陷的基础。当前的研究确定搜索策略分析可能是一种新的敏感评估方法,用于评估神经行为毒性。

更新日期:2020-06-25
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