Effects of co-exposure to lead and manganese on learning and memory deficits.
Effects of co-exposure to lead and manganese on learning and memory deficits.
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共同接触铅和锰对学习和记忆缺陷的影响
DOI：
10.1016/j.jes.2021.09.012
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发表时间：
2022-11
影响因子：
6.9
通讯作者：
Chen, Rui
中科院分区：
文献类型：
--
作者：
Guan, Ruili;Wang, Tao;Dong, Xiaoru;Du, Kejun;Li, Juan;Zhao, Fang;Xu, Jie;Li, Bin;Zheng, Gang;Shen, Xuefeng;Cao, Baohua;Wang, Jing;Aschner, Michael;Liu, Mingchao;Chen, Rui
铅 (Pb) 和锰 (Mn) 是常见的环境污染物，高接触量可能会导致神经毒性。然而，个体在现实生活中会受到共同暴露的影响，因此组合研究这些金属非常重要。断奶的 Sprague-Dawley 大鼠 (SD 大鼠) 随意饮用含有 Pb (100 ppm)、Mn (2.5 mg/mL) 或混合物的饮用水溶液，每种治疗都有其自己的米诺环素 (MC) (50 mg/Kg.d) 补充组。结果表明，在莫里斯水迷宫 (MWM) 和 Y 迷宫中，与对照组相比，所有暴露组的逃避潜伏期、目标象限花费的时间百分比和正确反应率均存在显着差异。与每个单一金属暴露组相比，组合暴露组表现出最显着的效果。与对照组相比，单一金属暴露组和联合暴露组的海马长时程增强（LTP）诱导水平显着降低。此外，联合暴露组的抑制作用显着大于单一金属暴露组。小胶质细胞在单独或组合暴露后第 3 天表现出激活，而星形胶质细胞在单独或组合暴露后第 5 天表现出激活，并伴有谷氨酸-谷氨酰胺循环相关蛋白 GLAST、GLT-1 和 GS 表达水平降低。此外，突触间隙中兴奋性神经递质谷氨酸的水平显着增加。当米诺环素抑制小胶质细胞的活化及其活化因子的释放时，星形胶质细胞的活化以及谷氨酸-谷氨酰胺循环相关蛋白GLAST、GLT-1和GS的表达均被逆转。此外，在米诺环素治疗后，每个暴露组的海马 LTP 诱导和认知损伤均显着减轻。而且，上述效果在联合暴露组中比在单一暴露组中更为显着。这些结果表明，与单一金属暴露组相比，铅和锰的联合暴露会对认知和突触可塑性产生更大的影响。其原因可能与小胶质细胞异常激活导致星形胶质细胞过度调节，导致星形胶质细胞谷氨酸重摄取功能障碍，导致认知和突触可塑性紊乱有关。
Lead (Pb) and manganese (Mn) are common environmental pollutants, with high exposures potentially resulting in neurotoxicity. However, individuals are subject to co-exposures in real life, and it is therefore important to study these metals in combination. Weaning Sprague-Dawley rats (SD rats) were given ad libitum access to drinking water solutions containing Pb (100 ppm), Mn (2.5 mg/mL) or a mixture, and each treatment has its own minocycline (MC) (50 mg/Kg.d) supplement group. The results showed that in the Morris water maze (MWM) and Y maze a significant difference in the escape latency, percent time spent in target quadrant and correct response ratio were noted in all exposure groups when compared to controls. The combined exposure group exhibited the most pronounced effect when compared with each of the single metal exposure groups. The induction levels of hippocampal long-term potentiation (LTP) were significantly reduced in the single metal and combined exposure groups compared to the control group. Furthermore, the inhibitory effects of combined exposure group were significantly greter than in the single metal exposure groups. Microglia displayed activation at day 3 after exposure alone or in combination, while astrocytes showed activation at day 5 after exposure alone or in combination, accompanied by decreased expression levels of glutamate-glutamine cycle-related proteins GLAST, GLT-1, and GS. Furthermore, the levels of the excitatory neurotransmitter glutamate in the synaptic cleft increased significantly. When microglial activation and release of its activated factors were inhibited by minocycline, the activation of astrocytes, and the expression of glutamate-glutamine cycle-related proteins GLAST, GLT-1, and GS were both reversed. In addition, upon minocycline treatment the induction of hippocampal LTP and the cognitive injury were significantly alleviated in each of the exposure groups. Moreover, the effects mentioned above were more significant in the combined exposure group than in the single exposure group. These results suggest that combined exposure to lead and manganese can cause greater effects on cognition and synaptic plasticity when compared to single metal exposure groups. And the reason may involve in microglia abnormal activation leading to an excessive regulation of astrocytes, resulting in glutamate reuptake dysfunction in astrocytes and lead to perturbed cognition and synaptic plasticity.
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影响因子：
3.8
作者：
Chen, JY;Tsao, GC;Zheng, W
通讯作者：
Zheng, W
影响因子：
4.2
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影响因子：
11.2
作者：
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通讯作者：
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作者：
Guilarte, Tomas R.;Chen, Ming-Kai;Schneider, Jay S.
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Schneider, Jay S.