Cellular and Molecular Neurobiology ( IF 3.6 ) Pub Date : 2022-06-05 , DOI: 10.1007/s10571-022-01237-0 Zeli Song 1 , Haoyue Mao 1 , Jinxuan Liu 1 , Wenchang Sun 1 , Shengwen Wu 1 , Xiaobo Lu 1 , Cuihong Jin 1 , Jinghua Yang 1
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Lanthanum (La) is a natural rare-earth element that can damage the central nervous system and impair learning and memory. However, its neurotoxic mechanism remains unclear. In this study, adult female rats were divided into 4 groups and given distilled water solution containing 0%, 0.125%, 0.25%, and 0.5% LaCl3, respectively, and this was done from conception to the end of the location. Their offspring rats were used to establish animal models to investigate LaCl3 neurotoxicity. Primary neurons cultured in vitro were treated with LaCl3 and infected with LKB1 overexpression lentivirus. The results showed that LaCl3 exposure resulted in abnormal axons in the hippocampus and primary cultured neurons. LaCl3 reduced the expression of LKB1, p-LKB1, STRAD and MO25 proteins, and directly or indirectly affected the expression of LKB1, leading to decreased activity of LKB1-MARK2 and LKB1-STK25-GM130 pathways. This study indicated that LaCl3 exposure could interfere with the normal effects of LKB1 in the brain and downregulate LKB1-MARK2 and LKB1-STK25-GM130 signaling pathways, resulting in abnormal axon in offspring rats.
Graphical Abstract
中文翻译：
氯化镧通过 LKB1-MARK2 和 LKB1-STK25-GM130 信号通路诱导轴突异常
镧 (La) 是一种天然稀土元素，可损害中枢神经系统并损害学习和记忆。然而，其神经毒性机制仍不清楚。本研究将成年雌性大鼠分为4组，分别给予含0%、0.125%、0.25%和0.5% LaCl 3的蒸馏水溶液，从受孕到定位结束。他们的后代大鼠被用来建立动物模型来研究LaCl 3 的神经毒性。体外培养的原代神经元用 LaCl 3处理并用 LKB1 过表达慢病毒感染。结果表明，LaCl 3暴露导致海马体和原代培养的神经元轴突异常。氯化镧3降低 LKB1、p-LKB1、STRAD 和 MO25 蛋白的表达，并直接或间接影响 LKB1 的表达，导致 LKB1-MARK2 和 LKB1-STK25-GM130 通路活性降低。本研究表明，LaCl 3暴露可干扰LKB1在大脑中的正常作用，下调LKB1-MARK2和LKB1-STK25-GM130信号通路，导致后代大鼠轴突异常。
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