Jin Cuihong, Gao Liang, Li Yingqi, Wu Shengwen, Lu Xiaobo, Yang Jinghua, Cai Yuan
Department of Toxicology, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
Jinzhou Medical University, No.40, Section III, Songpo Road, Linghe District, Jinzhou, 121000, People's Republic of China.
Exp Brain Res. 2017 Dec;235(12):3817-3832. doi: 10.1007/s00221-017-5102-5. Epub 2017 Oct 9.
Rare-earth elements (REEs) are applied in various fields by virtue of their superior physical and chemical properties. Surveys have reported that REEs can impair learning and memory in children and induce neurobehavioral abnormalities in animals. However, the mechanism underlying this neurotoxicity is still unclear. Lanthanum (La) is often chosen to study the effects of REEs. Here, we investigated the role of astrocyte-neuron lactate shuttle (ANLS) in spatial learning and memory impairment induced by LaCl in hippocampus, an important spatial memory-related brain region. Pregnant Wistar rats were exposed to 0, 0.125, 0.25, 0.5, or 1% LaCl in drinking water during pregnancy and lactation. After weaning, young rats continued to receive 0, 0.125, 0.25, 0.5, and 1% LaCl in the drinking water for 1 month. The results showed that LaCl exposure impaired the spatial learning and memory of rats in Morris water maze test, significantly reduced the mRNA and protein levels of glycogen synthetase, glycogen phosphorylase, lactate dehydrogenase A, monocarboxylate transporter 4, MCT-1, and MCT-2, and decreased total LDH activity and lactate contents in rat hippocampus. These results indicate that LaCl impairs spatial learning and memory in rats probably by suppressing ANLS in rat hippocampus. The study provides a novel clue of energy supply for neurons to clarify the neurotoxicity of REEs.
稀土元素（REEs）凭借其卓越的物理和化学性质而被应用于各个领域。调查报道称，REEs会损害儿童的学习和记忆，并在动物中诱发神经行为异常。然而，这种神经毒性的潜在机制仍不清楚。镧（La）常被选来研究REEs的影响。在此，我们研究了星形胶质细胞-神经元乳酸穿梭（ANLS）在由氯化镧（LaCl）诱导的海马体（一个与空间记忆相关的重要脑区）空间学习和记忆损伤中的作用。怀孕的Wistar大鼠在怀孕和哺乳期饮用含0、0.125、0.25、0.5或1% LaCl的水。断奶后，幼鼠继续饮用含0、0.125、0.25、0.5和1% LaCl的水1个月。结果表明，暴露于LaCl会损害大鼠在莫里斯水迷宫试验中的空间学习和记忆，显著降低糖原合成酶、糖原磷酸化酶、乳酸脱氢酶A、单羧酸转运蛋白4、MCT-1和MCT-2的mRNA和蛋白质水平，并降低大鼠海马体中的总乳酸脱氢酶活性和乳酸含量。这些结果表明，LaCl可能通过抑制大鼠海马体中的ANLS来损害大鼠的空间学习和记忆。该研究为阐明REEs的神经毒性提供了神经元能量供应的新线索。
