Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China.
Front Public Health. 2023 Aug 30;11:1247294. doi: 10.3389/fpubh.2023.1247294. eCollection 2023.
Fluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF-TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through experiments.
This study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting.
All rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities.
Currently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.
氟被认为是一种严重影响生物和生态系统的环境污染物，其危害性一直是公共卫生关注的焦点。氟的毒性作用包括细胞器损伤、氧化应激、细胞周期破坏、炎性因子分泌、细胞凋亡诱导和突触神经传递破坏。为了揭示氟中毒引起的脑损伤的机制，我们通过实验分析了氟中毒引起的脑损伤中 SIRT1 介导的 BDNF-TrkB 信号通路级联反应的分子机制和学习记忆功能。
本研究采用 50mg/L、100mg/L 和 150mg/L 氟化物构建了大鼠饮水型氟中毒模型，观察了大鼠氟斑牙的发生情况。随后，测量了大鼠血、尿、骨中氟含量，检测了大鼠学习记忆能力，并检测了氧化应激产物、炎性因子水平及乙酰胆碱酯酶（AchE）和胆碱乙酰转移酶（ChAT）活性。观察了大鼠骨骼和脑组织的病理结构变化，采用 Western blot 法测定 SIRT1、BDNF、TrkB 和凋亡蛋白水平。
氟暴露组大鼠均出现氟斑牙，学习记忆能力下降，尿氟、骨氟、血氟、氧化应激产物和炎性因子水平均高于对照组。氟暴露大鼠脑组织 AchE 和 ChAT 活性异常，海马神经元排列稀疏，细胞边界模糊，星形胶质细胞明显减少，细胞肿胀。此外，氟暴露大鼠脑组织核仁消失，神经元膜折叠，线粒体变形，嵴消失，空泡形成，染色质固缩、深染。氟暴露组 SIRT1、BDNF、TrkB 蛋白水平低于对照组，凋亡蛋白水平高于对照组，且与氟剂量密切相关。结果表明，过量氟可导致脑组织损伤，影响学习记忆能力。
目前，氟中毒引起的组织损伤尚无有效的治疗方法，因此，控制氟的摄入是预防和治疗氟中毒损伤的有效方法。
