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Cre-inducible Adeno Associated Virus-mediated Expression of P301L Mutant Tau Causes Motor Deficits and Neuronal Degeneration in the Substantia Nigra

dc.rights.licenseopenen_US
dc.contributor.authorYOU, Yang
dc.contributor.authorBOTROS, Mina
dc.contributor.authorENOO, Alicia
dc.contributor.authorBOCKMILLER, Aaron
dc.contributor.authorHERRON, Shawn
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorDELPECH, Jean-Christophe
dc.contributor.authorIKEZU, Tsuneya
dc.date.accessioned2021-09-27T08:37:10Z
dc.date.available2021-09-27T08:37:10Z
dc.date.issued2019-12
dc.identifier.issn0306-4522en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112396
dc.description.abstractEnAccumulation of microtubule associated protein tau in the substantia nigra is associated with several tauopathies including progressive supranuclear palsy (PSP). A number of studies have used mutant tau transgenic mouse model to mimic the neuropathology of tauopathies and disease phenotypes. However, tau expression in these transgenic mouse models is not specific to brain subregions, and may not recapitulate subcortical disease phenotypes of PSP. It is necessary to develop a new disease modeling system for cell and region-specific expression of pathogenic tau for modeling PSP in mouse brain. In this study, we developed a novel strategy to express P301L mutant tau to the dopaminergic neurons of substantia nigra by coupling tyrosine hydroxylase promoter Cre-driver mice with a Cre-inducible adeno-associated virus (iAAV). The results showed that P301L mutant tau was successfully transduced in the dopaminergic neurons of the substantia nigra at the presence of Cre recombinase and iAAV. Furthermore, the iAAV-tau-injected mice displayed severe motor deficits including impaired movement ability, motor balance, and motor coordination compared to the control groups over a short time-course. Immunochemical analysis revealed that tau gene transfer significantly resulted in loss of tyrosine hydroxylase-positive dopaminergic neurons and elevated phosphorylated tau in the substantia nigra. Our development of dopaminergic neuron-specific neurodegenerative mouse model with tauopathy will be helpful for studying the underlying mechanism of pathological protein propagation as well as development of new therapies.
dc.language.isoENen_US
dc.subject.enAdeno-associated virus
dc.subject.enMicrotubule-associated protein tau
dc.subject.enNeurodegenerative diseases
dc.subject.enSubstantia nigra
dc.subject.enTauopathies
dc.title.enCre-inducible Adeno Associated Virus-mediated Expression of P301L Mutant Tau Causes Motor Deficits and Neuronal Degeneration in the Substantia Nigra
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.neuroscience.2019.10.001en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed31689387en_US
bordeaux.journalNeuroscienceen_US
bordeaux.page65-74en_US
bordeaux.volume422en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.teamPsychoneuroimmunologie et Nutrition: Approches expérimentales et cliniquesen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Neuroscience&rft.date=2019-12&rft.volume=422&rft.spage=65-74&rft.epage=65-74&rft.eissn=0306-4522&rft.issn=0306-4522&rft.au=YOU,%20Yang&BOTROS,%20Mina&ENOO,%20Alicia&BOCKMILLER,%20Aaron&HERRON,%20Shawn&rft.genre=article


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