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胆碱通过α4β2 nAChRs 和 α7 nAChRs 缓解围产期氟暴露诱导的子代小鼠学习记忆损伤。

Choline alleviated perinatal fluoride exposure-induced learning and memory impairment through α4β2 nAChRs and α7 nAChRs in offspring mice.

机构信息

College of Veterinary Medicine, Shanxi Agricultural University, Taigu, China.

Science and Technology Research Center of China Customs, Beijing, China.

出版信息

Environ Toxicol. 2023 Mar;38(3):511-521. doi: 10.1002/tox.23692. Epub 2022 Oct 26.

DOI:10.1002/tox.23692
PMID:36286330
Abstract

Fluoride pollution is widely present in the living environment. As a critical period of brain development, the perinatal period is extremely vulnerable to fluoride. Studies have found that choline can protect the brain's memory and enhance the ability to focus. However, the effect of choline on perinatal fluoride-induced nerve damage remains unclear. Therefore, 32 Kunming newly conceived female mice and their offspring mice were randomly divided into control, NaF, LC + NaF, and HC + NaF groups, and the HE staining, Y-maze test, RT-PCR, western blotting, immunohistochemistry, etc. were used in this study. The results showed that fluoride decreased the brain organ coefficients and brain protein content (p < 0.05, p < 0.01), and caused histomorphological damage in the hippocampus and cortex, which suggested that fluoride affected the development of the brain and damaged the brain. Moreover, the results of the Y-maze test showed that fluoride increased the number of learning days, error reaction time, and total reaction time, and decreased the AchE activity in the brain (p < 0.05, p < 0.01), which indicated that fluoride reduced the learning and memory ability of the mice. Besides, the results showed that fluoride decreased the mRNA and protein expression levels of α4β2 nAChRs and α7 nAChRs in the hippocampus and cortex (p < 0.05, p < 0.01). However, perinatal choline supplementation reversed the aforementioned fluoride-induced changes. In short, these results demonstrated that choline alleviated perinatal fluoride-induced learning and memory impairment, which will provide a rationale for the mitigation and prevention of fluoride-induced brain damage.

摘要

氟污染广泛存在于生活环境中。围生期是大脑发育的关键时期,极易受到氟的影响。研究发现,胆碱能保护大脑记忆,增强注意力。然而,胆碱对围生期氟诱导的神经损伤的影响尚不清楚。因此,本研究将 32 只昆明新受孕雌性小鼠及其仔鼠随机分为对照组、NaF 组、LC+NaF 组和 HC+NaF 组,采用 HE 染色、Y 迷宫实验、RT-PCR、western blot、免疫组织化学等方法。结果表明,氟降低了脑器官系数和脑蛋白含量(p<0.05,p<0.01),并导致海马和皮质的组织形态学损伤,表明氟影响了大脑的发育并损害了大脑。此外,Y 迷宫实验结果表明,氟增加了学习天数、错误反应时间和总反应时间,降低了脑内乙酰胆碱酯酶(AchE)活性(p<0.05,p<0.01),表明氟降低了小鼠的学习和记忆能力。此外,结果表明氟降低了海马和皮质中α4β2 nAChRs 和 α7 nAChRs 的 mRNA 和蛋白表达水平(p<0.05,p<0.01)。然而,围生期补充胆碱可逆转上述氟诱导的变化。总之,这些结果表明胆碱缓解了围生期氟诱导的学习和记忆障碍,为减轻和预防氟诱导的脑损伤提供了依据。

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