Qi Wang, Li Ying, Fude Huang, Jingya Lin, Wenan Wang
{"title":"tau蛋白对阿尔茨海默病果蝇a β诱导的突触损伤的影响。","authors":"Qi Wang, Li Ying, Fude Huang, Jingya Lin, Wenan Wang","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The etiology and pathologic mechanism underlying Alzheimer's disease (AD) are not clear. This study determined the effects of tau on amyloid-beta peptide(Aβ)-induced synaptic damages in a Drosophila model of AD.</p><p><strong>Methods: </strong>Galactose-regulated upstream promoter element 4(Gal4) and an upstream active sequence system was used to establish four kinds of Aβ transgenic Drosophila models of AD. Behavioral evaluation and immunohistochemical localization were performed in Aβ transgenic Drosophila models. Tau mutants were introduced into arctic mutant Aβ1-42 (arctic mutant Aβ [Aβarc]) Drosophila. The P{Gal4}A307 Drosophila strain was used as a control group; 12 strains were obtained to determine the effects of tau with or without Aβarc. Electrophysiologic records of the tau mutant groups were created.</p><p><strong>Results: </strong>The flight and crawling ability of Aβ transgenic Drosophila were gradually weakened compared to the control group, and the life span was significantly shorter than the control group. Aβ was specifically expressed in the Drosophila giant fiber pathway and further accumulated in neuronal cell bodies based on immunohistochemistry. The percentage of the excitatory junctional potential (EJP) response in transgenic Drosophila expressing Aβarc was significantly decreased, which was approximately 40% lower than the control group. The tau deletion mutation alleviated the synaptic transmission disorder caused by Aβ and improved the viability of Drosophila.</p><p><strong>Conclusion: </strong>The tau deletion mutation significantly improved the synaptic damage caused by Aβ, and tau protein played an indispensable role in the synaptic dysfunction caused by Aβ, suggesting that Aβ and tau have close interactions in the pathogenesis of AD.</p>","PeriodicalId":19098,"journal":{"name":"Neuro endocrinology letters","volume":null,"pages":null},"PeriodicalIF":0.6000,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of tau on Aβ-induced synaptic damage in a Drosophila model of Alzheimer's disease.\",\"authors\":\"Qi Wang, Li Ying, Fude Huang, Jingya Lin, Wenan Wang\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The etiology and pathologic mechanism underlying Alzheimer's disease (AD) are not clear. This study determined the effects of tau on amyloid-beta peptide(Aβ)-induced synaptic damages in a Drosophila model of AD.</p><p><strong>Methods: </strong>Galactose-regulated upstream promoter element 4(Gal4) and an upstream active sequence system was used to establish four kinds of Aβ transgenic Drosophila models of AD. Behavioral evaluation and immunohistochemical localization were performed in Aβ transgenic Drosophila models. Tau mutants were introduced into arctic mutant Aβ1-42 (arctic mutant Aβ [Aβarc]) Drosophila. The P{Gal4}A307 Drosophila strain was used as a control group; 12 strains were obtained to determine the effects of tau with or without Aβarc. Electrophysiologic records of the tau mutant groups were created.</p><p><strong>Results: </strong>The flight and crawling ability of Aβ transgenic Drosophila were gradually weakened compared to the control group, and the life span was significantly shorter than the control group. Aβ was specifically expressed in the Drosophila giant fiber pathway and further accumulated in neuronal cell bodies based on immunohistochemistry. The percentage of the excitatory junctional potential (EJP) response in transgenic Drosophila expressing Aβarc was significantly decreased, which was approximately 40% lower than the control group. The tau deletion mutation alleviated the synaptic transmission disorder caused by Aβ and improved the viability of Drosophila.</p><p><strong>Conclusion: </strong>The tau deletion mutation significantly improved the synaptic damage caused by Aβ, and tau protein played an indispensable role in the synaptic dysfunction caused by Aβ, suggesting that Aβ and tau have close interactions in the pathogenesis of AD.</p>\",\"PeriodicalId\":19098,\"journal\":{\"name\":\"Neuro endocrinology letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.6000,\"publicationDate\":\"2022-06-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuro endocrinology letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro endocrinology letters","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Effects of tau on Aβ-induced synaptic damage in a Drosophila model of Alzheimer's disease.
Objectives: The etiology and pathologic mechanism underlying Alzheimer's disease (AD) are not clear. This study determined the effects of tau on amyloid-beta peptide(Aβ)-induced synaptic damages in a Drosophila model of AD.
Methods: Galactose-regulated upstream promoter element 4(Gal4) and an upstream active sequence system was used to establish four kinds of Aβ transgenic Drosophila models of AD. Behavioral evaluation and immunohistochemical localization were performed in Aβ transgenic Drosophila models. Tau mutants were introduced into arctic mutant Aβ1-42 (arctic mutant Aβ [Aβarc]) Drosophila. The P{Gal4}A307 Drosophila strain was used as a control group; 12 strains were obtained to determine the effects of tau with or without Aβarc. Electrophysiologic records of the tau mutant groups were created.
Results: The flight and crawling ability of Aβ transgenic Drosophila were gradually weakened compared to the control group, and the life span was significantly shorter than the control group. Aβ was specifically expressed in the Drosophila giant fiber pathway and further accumulated in neuronal cell bodies based on immunohistochemistry. The percentage of the excitatory junctional potential (EJP) response in transgenic Drosophila expressing Aβarc was significantly decreased, which was approximately 40% lower than the control group. The tau deletion mutation alleviated the synaptic transmission disorder caused by Aβ and improved the viability of Drosophila.
Conclusion: The tau deletion mutation significantly improved the synaptic damage caused by Aβ, and tau protein played an indispensable role in the synaptic dysfunction caused by Aβ, suggesting that Aβ and tau have close interactions in the pathogenesis of AD.
期刊介绍:
Neuroendocrinology Letters is an international, peer-reviewed interdisciplinary journal covering the fields of Neuroendocrinology, Neuroscience, Neurophysiology, Neuropsychopharmacology, Psychoneuroimmunology, Reproductive Medicine, Chronobiology, Human Ethology and related fields for RAPID publication of Original Papers, Review Articles, State-of-the-art, Clinical Reports and other contributions from all the fields covered by Neuroendocrinology
Letters.
Papers from both basic research (methodology, molecular and cellular biology, anatomy, histology, biology, embryology, teratology, normal and pathological physiology, biophysics, pharmacology, pathology and experimental pathology, biochemistry, neurochemistry, enzymology, chronobiology, receptor studies, endocrinology, immunology and neuroimmunology, animal physiology, animal breeding and ethology, human ethology, psychology and others) and from clinical research (neurology, psychiatry and child psychiatry, obstetrics and gynecology, pediatrics, endocrinology, immunology, cardiovascular studies, internal medicine, oncology and others) will be considered.
The Journal publishes Original papers and Review Articles. Brief reports, Special Communications, proved they are based on adequate experimental evidence, Clinical Studies, Case Reports, Commentaries, Discussions, Letters to the Editor (correspondence column), Book Reviews, Congress Reports and other categories of articles (philosophy, art, social issues, medical and health policies, biomedical history, etc.) will be taken under consideration.