跨膜蛋白Teneurin-1在氟致神经细胞突触损伤中的作用研究

氟是自然界广泛存在的一种元素，过量摄入可扰乱人和动物神经系统稳态。目前普遍认为氟暴露可使神经突触结构与功能改变，但机制不明。课题前期研究表明氟能引起小鼠学习记忆能力下降，神经突触数量显著减少；进一步发现调控突触发育的跨膜蛋白Teneurin-1的表达在氟暴露细胞中被抑制。Teneurin-1是否参与氟致神经细胞突触损伤过程？本项目拟利用小鼠和HT-22细胞建立氟中毒模型，探讨氟暴露模型中Teneurin-1动态变化及突触结构和功能损伤情况；采用基因重组技术，探究Teneurin-1过表达对氟致神经细胞突触功能损伤的拮抗效果；利用si-RNA沉默Teneurin-1，检测氟暴露神经细胞突触结构与功能变化，从正反两方面论证Teneurin-1对氟暴露神经细胞突触结构与功能损伤的调控作用。本项目以突触损伤为切入点，探索Teneurin-1在氟神经毒性中的作用机制，为氟中毒的治疗与防控提供新思路。

Fluoride is considered as an essential trace element that is ubiquitously present in environment. Prolonged exposure to fluoride is known to disrupt the homeostasis of nervous system, which can alter the structure and function of synapses. However, the exact mechanisms of F-induced neurotoxicity are not clearly defined. Our previous study showed that fluoride exposure decreased the learning and memory ability of offspring mice, and reduced the number of synapses. Furthermore, the expression of Teneurin-1 was significantly decreased in NaF-exposed cells. Is there a direct correlation between the synaptic toxicity of fluoride and decreased expression of Teneurin-1? In this study, ICR mice and HT-22 cells will be selected to establish fluorosis model to investigate the dynamic changes of teneurin-1 and damages of synapse. The gene recombination technology will be used to explore the antagonism of Teneurin-1 in synaptic injury caused by fluoride in vitro. Moreover, RNA silencing is used to investigate the changes of synaptic morphology and function. In order to explain the regulatory effects of Teneurin-1 on synaptic damages induced by fluoride. The study, which uses synaptic damage as the innovation point to assess the effects of Teneurin-1 on the structure and function of synapse induced by fluoride, will provide a novel idea for the treatment and prevention of fluorosis.