氟化物过量摄入对阿尔茨海默病发病的影响及其细胞分子机制

Effects of fluoride over-intake on the pathogenesis of Alzheimer’s disease and its cellular and molecular mechanisms

氟离子是哺乳动物体内的微量元素,普遍存在于生活环境之中。氟化物在人体内的安全范围窄,过量摄入可能有损健康甚至导致严重疾病。体外细胞系实验揭示,氟化物能引起细胞线粒体损伤、能量代谢障碍和氧化应激水平升高。在体实验显示,不同品系的大、小鼠给予过量的氟化物会降低动物的空间学习记忆能力,并产生阿尔茨海默病(Alzheimer’s disease,AD)样的病理改变,包括脑中小胶质细胞激活、炎性细胞因子释放、突触密度降低、谷氨酸与乙酰胆碱的神经传递紊乱等。在APP/PS1转基因小鼠模型上,给予氟化物增加了β淀粉样蛋白(amyloid-β,Aβ)沉积、tau蛋白过磷酸化和促进神经元变性等。本文从细胞和亚细胞至在体功能水平系统地分析氟化物过量摄入所产生的神经病理效应,以期从环境因素入手为群体性降低AD发病提供一条新思路。

Fluoride ion is a trace element in mammalians and is ubiquitously existed in the living environment.The safe range of fluoride in the human body is narrow,and excessive intake can be harmful to health or even lead to serious illness.In vitro experiments on cell lines revealed that fluoride can cause mitochondrial damage,energy metabolism dysfunction and elevated oxidative stress.In vivo studies in different strains of rats and mice have shown that excessive fluoride could impair the spatial learning and memory,and trigger Alzheimer’s disease(AD)like-pathological changes,including the activation of microglial cells,the release of inflammatory cytokines,the reduction of synaptic density,and the impaired glutaminergic and cholinergic neurotransmission.In the APP/PS1 transgenic mouse model,fluoride administration also promoted Aβdeposition,tau hyperphosphorylation and neurodegeneration.Taken together,we analyzed and discussed the neuropathological effects of fluoride over-intake at cellular and systematic levels,with a view to providing a new route for populational prevention of AD by controlling etiological environmental factors.