氯化镧通过上调 miR-124 的表达并靶向 PIK3CA 来调节 PI3K/Akt 信号通路，从而导致大鼠神经毒性。
Lanthanum Chloride Causes Neurotoxicity in Rats by Upregulating miR-124 Expression and Targeting PIK3CA to Regulate the PI3K/Akt Signaling Pathway.
机构信息
Institute of Molecular Medicine, Medical School, Eastern Liaoning University, Dandong Liaoning 118003, China.
Department of Nursing, Medical School, Eastern Liaoning University, Dandong Liaoning 118003, China.
出版信息
Biomed Res Int. 2020 May 5;2020:5205142. doi: 10.1155/2020/5205142. eCollection 2020.
BACKGROUND
Lanthanum (La) exposure can cause central nervous system (CNS) damage and dysfunction in children, seriously affecting intellectual development. miR-124 plays an important role in the development of the nervous system. We exposed rats to a La environment then observed the rats' learning and memory damage and neurotoxicity and the relationship with miR-124.
METHODS
Rats were exposed to LaCl via drinking water. The rats' offspring were exposed to LaCl from their mother before weaning, then from La water for 28 days. A Morris water maze was used to observe spatial memory capabilities. H&E staining and TUNEL assays were used to observe pathological changes and apoptosis in the hippocampus. miR-124 was detected by RT-qPCR, and its targeting was confirmed by luciferase assay. The HT22 cell line was cultured with LaCl and treated with miR-124 mimics or inhibitors; then, expression of PI3K/Akt-related proteins was detected by western blot.
RESULTS
La exposure can lead to impaired learning and memory ability in offspring. Offspring with La accumulations in the hippocampus showed severe damage, disordered cells, and increased neurocyte apoptosis. In vitro, the postsynaptic density protein 95 was downregulated under La exposure and apoptosis increased. This effect of La can be attenuated by miR-124 inhibitors and enhanced by miR-124 mimics. LaCl exposure increased miR-124 expression and targeting on PIK3CA, downregulating PI3K, p-Akt, and p-NF-B p65.
CONCLUSION
La causes neurotoxicity by upregulating miR-124 expression and targeting PIK3CA through the PI3K/Akt signaling pathway.
背景
镧（La）暴露可导致儿童中枢神经系统（CNS）损伤和功能障碍，严重影响智力发育。miR-124 在神经系统发育中发挥重要作用。我们将大鼠暴露于 La 环境中，然后观察大鼠的学习和记忆损伤以及神经毒性及其与 miR-124 的关系。
方法
大鼠通过饮用水暴露于 LaCl。大鼠的后代在断奶前从母亲那里开始暴露于 LaCl，然后在 La 水中暴露 28 天。Morris 水迷宫用于观察空间记忆能力。H&E 染色和 TUNEL 检测用于观察海马的病理变化和细胞凋亡。通过 RT-qPCR 检测 miR-124，通过荧光素酶检测证实其靶标。培养 HT22 细胞系，用 LaCl 处理并用 miR-124 模拟物或抑制剂处理；然后，通过 Western blot 检测 PI3K/Akt 相关蛋白的表达。
结果
La 暴露可导致后代学习和记忆能力受损。海马中 La 积累的后代表现出严重损伤、细胞紊乱和神经细胞凋亡增加。在体外，La 暴露下调了突触后密度蛋白 95，增加了细胞凋亡。La 模拟物可以减弱 miR-124 抑制剂的这种作用，增强 miR-124 模拟物的作用。LaCl 暴露增加了 miR-124 的表达并靶向 PIK3CA，下调了 PI3K、p-Akt 和 p-NF-B p65。
结论
La 通过上调 miR-124 的表达并通过 PI3K/Akt 信号通路靶向 PIK3CA 导致神经毒性。
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