Dopamine D2 Receptor Stimulation Potentiates PolyQ-Huntingtin-Induced Mouse Striatal Neuron Dysfunctions via RhoROCK-II Activation 英文参考文献.docVIP

下载本文档

1
0
约4.96万字
约 11页
2017-05-11 发布于上海
举报
版权申诉

Dopamine D2 Receptor Stimulation Potentiates PolyQ-Huntingtin-Induced Mouse Striatal Neuron Dysfunctions via RhoROCK-II Activation 英文参考文献.doc

1、本文档共11页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Dopamine D2 Receptor Stimulation Potentiates PolyQ-Huntingtin-Induced Mouse Striatal Neuron Dysfunctions via RhoROCK-II Activation 英文参考文献

DopamineD2ReceptorStimulationPotentiatesPolyQ- Huntingtin-InducedMouseStriatalNeuronDysfunctions viaRho/ROCK-IIActivation CaroleDeyts1,2,3,BeatrizGalan-Rodriguez1,2,ElodieMartin1,2,NicolasBouveyron1,2 ,Emmanuel Roze1,2,4,DelphineCharvin1,2,JocelyneCaboche1,2.,SandrineBe′tuing1,2,5. * 1CNRS UMR 7102, Universite′ Pierre et Marie Curie-Paris 6, Paris, France, 2INSERM UMRS 952, CNRS UMR 7224, Universite′ Pierre et Marie Curie-Paris 6, Paris, France, 3BiologicalSciencesDivision,UniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica,4ServicedeNeurologie,Ho?pitalSalpe?trie`re,AssitancePublique-Ho?pitaux deParis,Paris,France,5Universite′ EvryVald’Essonne,Evry,France Abstract Background: Huntington’s disease (HD) is a polyglutamine-expanded related neurodegenerative disease. Despite the ubiquitousexpressionofexpanded,polyQ-Huntingtin(ExpHtt)inthebrain,striatalneuronspresentahighersusceptibility to the mutation. A commonly admitted hypothesis is that Dopaminergic inputs participate to this vulnerability. We previouslyshowedthatD2receptorstimulationincreasedaggregateformationandneuronaldeathinducedbyExpHttin primarystriatalneuronsinculture,andchronicD2antagonisttreatmentprotectsstriataldysfunctionsinducedbyExpHttin alentiviral-inducedmodelsysteminvivo.Thepresentworkwasdesignedtoelucidatethesignallingpathwaysinvolved, downstreamD2receptor(D2R)stimulation,instriatalvulnerabilitytoExpHtt. Methodology/Principal Findings: Using primary striatal neurons in culture, transfected with a tagged-GFP version of humanexon1ExpHtt,andsiRNAsagainstD2RorD1R,weconfirmthatDApotentiatesneuronaldysfunctionsviaD2Rbut notD1Rstimulation.WedemonstratethatD2agonisttreatmentinducesneuriticretractionandgrowthconecollapsein Htt-andExpHttexpressingneurons.WethentestedapossibleinvolvementoftheRho/ROCKsignallingpathway,which playsakeyroleinthedynamicofthecytoskeleton,intheseprocesses.ThepharmacologicalinhibitorsofROCK(Y27632and Hydroxyfasudil), as well as siRNAs against ROCK-II, reversed D2-related e