神经病靶酯酶（NTE）（生理底物为卵磷脂/溶血卵磷脂）活性的抑制是有机磷引起的迟发性神经毒性（OPIDN）发生的起始步骤，但NTE被抑制后下游的生化事件发生什么样的变化及其如何导致神经损伤的发生却一直未曾知晓。本项目围绕神经轴突尤其是雪旺氏细胞内质网（ER）磷脂组份及囊泡运输功能在接触神经毒性有机磷后发生的变化开展深入研究，以揭示ER磷脂稳态失衡后囊泡运输功能紊乱与OPIDN的关系。成年鸡因对OPIDN敏感而作为动物模型，结合构建的鸡神经髓鞘/雪旺氏细胞体外模型，检测ER应激与囊泡运输状态，了解ER磷脂失衡导致囊泡运输紊乱与神经损伤的关系，并结合在雪旺氏细胞上对NTE进行敲除或过表达研究揭示NTE表达水平与雪旺氏细胞磷脂稳态与囊泡运输的关系。进一步验证ER应激是否介导囊泡运输紊乱在OPIDN中的作用，从而揭示NTE被有机磷抑制后如何引发神经轴突损伤，以进一步明确OPIDN发生的分子机理。

The inhibition of neuropathy target esterase (NTE) that is capable of catalyzing the degradation of the substances phosphatidylcholine and lysophosphocholine, is regarded as the initial step of the organophosphate-induced delayed neuropathy (OPIDN), but the biochemical cascades in the downstream after the NTE inhibition, which could lead to the damage of axons and the long axons in peripheral nervous system in particular were still unknown. This proposal is to investigate the mechanisms of OPIDN by studying the role of vesicle trafficking disorder. The effect of tri-o-cresyl phosphate (TOCP), a neuropathic organophosphate on changes of ER phospholipids patterns in adult hen and the myelination model generated from the co-culture of the Schwann cells and motoneurons isolated from chick embryo, and the Schwann cell line sNF96.2 cells, are studied. Correlation of endoplasmic reticulum stress (ERS) and vesicle trafficking disorder induced by the imbalance of phospholipids in the OPIDN animal and the tested cells are further investigated. In addition, pharmacological method will be used to confirm the hypothesis. The results of this study will reveal how TOCP-modified NTE lead to the disorder of vesicle trafficking, and then finally caused the damage of the axons and the myelination, which will help us to further understand the detailed neurobiochemical mechanism of OPIDN.