Lanthanum is one of REEs documented to have neurotoxicity that led to learning and memory ability impairments. However, the mechanisms underlying La-induced neurotoxicity remain largely unexplored. Autophagy is a self-balancing and self-renewal process that degrades damaged organelles and macromolecules through lysosomal pathway. Importantly, appropriate autophagy levels have protective effects against harmful stress, while excessive autophagy has been demonstrated to be implicated in neurological diseases. ER is close to mitochondria at specific sites with a reported distance of 10–30 nm. The functional domains between the two organelles, called MAM, have been associated with autophagosome synthesis. In this study, the pregnant Wistar rats were randomly divided into four groups and given distilled water solution containing 0%, 0.125%, 0.25%, and 0.5% LaCl₃ for drinking during gestation and lactation. The pups were exposed to LaCl₃ via the maternal placenta and three-week lactation. Experimental results showed that LaCl₃ decreased spatial learning and memory ability of offspring rats, decreased tethering protein complexes expression of MAM, damaged MAM structure, up-regulated NOX4 expression which led to active ROS-AMPK-mTOR signaling pathway. Our findings suggest that decreased spatial learning and memory ability induced by LaCl₃ may be related to the abnormally autophagy regulated by tethering protein complexes of MAM.

镧是一种被证明具有神经毒性的稀土元素，可导致学习和记忆能力受损。然而，La 诱导的神经毒性的机制在很大程度上仍未探索。自噬是一种自我平衡和自我更新的过程，通过溶酶体途径降解受损的细胞器和大分子。重要的是，适当的自噬水平对有害压力具有保护作用，而过度自噬已被证明与神经系统疾病有关。ER 在特定位点靠近线粒体，据报道距离为 10-30 nm。两个细胞器之间的功能域，称为 MAM，与自噬体合成有关。本研究将孕Wistar大鼠随机分为4组，分别给予含0%、0.125%、0.25%、₃孕期和哺乳期饮用。幼崽通过母体胎盘和三周哺乳期暴露于 LaCl _{3 。}实验结果表明，LaCl ₃降低了后代大鼠的空间学习和记忆能力，降低了MAM的束缚蛋白复合物表达，破坏了MAM结构，上调了NOX4的表达，导致ROS-AMPK-mTOR信号通路活跃。我们的研究结果表明，LaCl ₃诱导的空间学习和记忆能力下降可能与 MAM 束缚蛋白复合物调控的异常自噬有关。