Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
J Environ Sci (China). 2022 Nov;121:65-76. doi: 10.1016/j.jes.2021.09.012. Epub 2022 Feb 1.
Lead (Pb) and manganese (Mn) are common neurotoxins. 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 were given ad libitum access to drinking water solutions containing Pb (100 mg/L), Mn (2.5 mg/mL) or a mixture, and each treatment had its own minocycline (50 mg/(kg•day)) supplement group. The results showed a significant difference in spatial memory and induction levels of hippocampal long-term potentiation (LTP) in all exposure groups when compared with controls. The combined-exposure group exhibited the most pronounced effect when compared with each of the single-metal exposure groups. Microglia displayed activation at day 3 after exposure alone or in combination, while astrocytes showed activation at day 5, accompanied by decreased expression levels of GLAST, GLT-1, and GS. Furthermore, the levels of glutamate in the synaptic cleft increased significantly. When microglial activation was inhibited by minocycline, the activation of astrocytes and the expression of GLAST, GLT-1, and GS were both reversed. In addition, upon minocycline treatment, hippocampal LTP impairment and cognitive injury were significantly alleviated in each of the exposure groups. These results suggest that combined exposure to Pb and Mn can cause greater effects on cognition and synaptic plasticity when compared to single-metal exposure groups. The reason may involve abnormal activation of microglia leading to excessive regulation of astrocytes, resulting in glutamate reuptake dysfunction in astrocytes and leading to perturbed cognition and synaptic plasticity.
铅（Pb）和锰（Mn）是常见的神经毒素。然而，在现实生活中，个体可能会同时接触到这些金属，因此研究它们的联合暴露非常重要。我们对断奶的 Sprague-Dawley 大鼠进行了自由饮水实验，水内含有 Pb（100mg/L）、Mn（2.5mg/mL）或混合物，并且每个处理组都有自己的二甲胺四环素（50mg/（kg•天））补充组。结果表明，与对照组相比，所有暴露组的空间记忆和海马长时程增强（LTP）诱导水平都有显著差异。与单一金属暴露组相比，联合暴露组的效果最为显著。单独或联合暴露 3 天后，小胶质细胞被激活，而星形胶质细胞在暴露 5 天后被激活，同时 GLAST、GLT-1 和 GS 的表达水平下降。此外，突触间隙中的谷氨酸水平显著升高。当用二甲胺四环素抑制小胶质细胞的激活时，星形胶质细胞的激活以及 GLAST、GLT-1 和 GS 的表达都得到了逆转。此外，在用二甲胺四环素治疗后，每个暴露组的海马 LTP 损伤和认知损伤都得到了显著缓解。这些结果表明，与单一金属暴露组相比，Pb 和 Mn 的联合暴露对认知和突触可塑性的影响更大。原因可能涉及小胶质细胞的异常激活导致星形胶质细胞的过度调节，导致星形胶质细胞中谷氨酸摄取功能障碍，从而导致认知和突触可塑性紊乱。
