敲低神经靶酯酶引起斑马鱼发育缺陷  

Knocking Down the Neuropthy Target Esterase Causes DevelopmentalDefects in Zebrafish

作　　者：唐思敏 秦晓旭 王家英 徐晓悦 薄文飞 李凤 纪鹏 董小雷[1] 宋扬[1] 王磊 TANG Si-Min;QIN Xiao-Xu;WANG Jia-Ying;XU Xiao-Yue;BO Wen-Fei;LI Feng;JI Peng;DONG Xiao-Lei;SONG Yang;WANG Lei(School of Bioengineering,State Key Laboratory,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250353,China;Department of Quality,Jinan Haopu Biotechnology Co.,Ltd,Jinan 250101,China;Department of Quality Management,Jinan Vitality Food Co.,Ltd,Jinan 250300,China;Qilu Children’s Hospital,Anesthesiology Department,Jinan 250300,China)

机构地区：[1]齐鲁工业大学(山东省科学院)生物工程学院国家重点实验室,济南250353 [2]济南皓普生物技术有限公司质检部,济南250101 [3]济南活力食品有限公司质量管理部,济南250300 [4]济南市儿童医院麻醉科室,济南250300

出　　处：《中国生物化学与分子生物学报》2023年第10期1487-1493,共7页Chinese Journal of Biochemistry and Molecular Biology

摘　　要：神经靶酯酶是Patatin样磷脂酶家族的成员,在神经发育中发挥重要作用。某些有机磷通过抑制神经靶标酯酶,导致人类和鸡有机磷酸酯诱导的迟发性神经病。神经靶标酯酶突变还会导致遗传性痉挛性截瘫等运动神经元疾病。Neuropthy target esterase功能的重要性已经得到一些了解,但是对于NTE在动物发育过程中的具体功能以及其导致运动神经元疾病的具体机制尚不清楚。本次实验对nte在斑马鱼发育过程中表达情况进行了分析,在此基础上使用吗啉反义寡核苷酸敲低nte基因,研究nte在斑马鱼胚胎中的具体功能及其作用机制。结果表明,nte出现在胚胎发育早期,并且斑马鱼Nte在其胚胎发育整个过程中表达。nte敲低后的斑马鱼表现出一系列的发育缺陷,包括尾部卷曲、轴突截断和分叉。nte敲低的斑马鱼胚胎细胞凋亡增加,神经元中出现胞内空泡、异常膜结构积累、内质网和线粒体结构异常以及自噬增加。总之,NTE在动物发育过程中以及其导致的运动神经元疾病中发挥重要作用。本研究为NTE的功能及其在神经变性中的作用机制提供了依据。Neuropthy target esterase(NTE)is a member of the patatin-like phospholipase(PNPLA)family and is reported to play an important role in neurodevelopment.NTE inhibition by some certain types of organophosphorus(OP)leads to delayed neuropathy(OPIDN)in humans and hens.NTE mutations also cause hereditary spastic paraplegia in motor neuron diseases.The importance of NTE function has been understood,but the specific function of NTE in animal development and motor neuron diseases are still unclear.Here we analyze the expression of nte during the development of zebrafish.On this basis,we used morpholine antisense oligonucleotides to knock down the nte gene to study its specific function and mechanism in zebrafish embryos.The results showed that nte appeared at the early stage of embryonic development,and zebrafish Nte was expressed throughout the embryonic development.nte-knockdown showed a range of developmental defects,including tail curling,axon truncation,and branching.Furthermore,we found neurons in nte knockdown zebrafish embryos displayed intracellular vacuoles,abnormal accumulation of membrane structures,abnormal structure of endoplasmic reticulum and mitochondria,and increased autophagy.In conclusion,NTE plays an important role in animal development and the motor neuron diseases.Our research provides new insights into NTE functions and a possible mechanism related to neurodegeneration.

关 键 词：神经靶酯酶 吗啉反义寡核苷酸 斑马鱼 自噬 

分 类 号：R741.02[医药卫生—神经病学与精神病学]