Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons

DC FieldValueLanguage
dc.contributor.authorKadkhodaei, Banafsheh-
dc.contributor.authorIto, Takehito-
dc.contributor.authorJoodmardi, Eliza-
dc.contributor.authorMattsson, Bengt-
dc.contributor.authorRouillard, Claude-
dc.contributor.authorCarta, Manolo-
dc.contributor.authorMuramatsu, Shin-Ichi-
dc.contributor.authorSumi-Ichinose, Chiho-
dc.contributor.authorNomura, Takahide-
dc.contributor.authorMetzger, Daniel-
dc.contributor.authorChambon, Pierre-
dc.contributor.authorLindqvist, Eva-
dc.contributor.authorLarsson, Nils-Göran-
dc.contributor.authorOlson, Lars-
dc.contributor.authorBjörklund, Anders-
dc.contributor.authorIchinose, Hiroshi-
dc.contributor.authorPerlmann, Thomas-
dc.date.accessioned2018-02-12T13:32:17Z-
dc.date.available2018-02-12T13:32:17Z-
dc.date.issued2009-12-16-
dc.identifier.issn0270-6474fr
dc.identifier.urihttp://hdl.handle.net/20.500.11794/17001-
dc.description.abstractTranscription factors involved in the specification and differentiation of neurons often continue to be expressed in the adult brain, but remarkably little is known about their late functions. Nurr1, one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood. In Parkinson's disease, Nurr1 expression is diminished and mutations in the Nurr1 gene have been identified in rare cases of disease; however, the significance of these observations remains unclear. Here, a mouse strain for conditional targeting of the Nurr1 gene was generated, and Nurr1 was ablated either at late stages of mDA neuron development by crossing with mice carrying Cre under control of the dopamine transporter locus or in the adult brain by transduction of adeno-associated virus Cre-encoding vectors. Nurr1 deficiency in maturing mDA neurons resulted in rapid loss of striatal DA, loss of mDA neuron markers, and neuron degeneration. In contrast, a more slowly progressing loss of striatal DA and mDA neuron markers was observed after ablation in the adult brain. As in Parkinson's disease, neurons of the substantia nigra compacta were more vulnerable than cells in the ventral tegmental area when Nurr1 was ablated at late embryogenesis. The results show that developmental pathways play key roles for the maintenance of terminally differentiated neurons and suggest that disrupted function of Nurr1 and other developmental transcription factors may contribute to neurodegenerative disease.fr
dc.languageengfr
dc.publisherSociety for Neurosciencefr
dc.titleNurr1 is required for maintenance of maturing and adult midbrain dopamine neuronsfr
dc.typeCOAR1_1::Texte::Périodique::Revue::Contribution à un journal::Article::Article de recherchefr
dcterms.bibliographicCitationThe Journal of neuroscience, Vol. 29 (50), 15923-15932 (2009)fr
dc.identifier.doi10.1523/JNEUROSCI.3910-09.2009fr
dc.identifier.pubmed20016108fr
dc.subject.rvmDopaminefr
dc.subject.rvmFacteurs de transcriptionfr
dc.subject.rvmMésencéphalefr
dc.subject.rvmNeuronesfr
rioxxterms.versionVersion of Recordfr
rioxxterms.version_of_recordhttp://dx.doi.org/10.1523/JNEUROSCI.3910-09.2009fr
rioxxterms.project.funder_nameMichael J. Fox Foundation for Parkinson's Researchfr
rioxxterms.project.funder_nameVetenskapsrådet via Linné Center DBRMfr
rioxxterms.project.funder_nameHuman Frontier Science Programfr
rioxxterms.project.funder_nameMinistry of Education, Culture, Sports, Science, and Technology of Japanfr
rioxxterms.project.funder_nameMinistry of Health, Labor, and Welfare of Japanfr
rioxxterms.project.funder_nameJapan Science and Technology Agency, Core Research for Evolutional Science and Technologyfr
rioxxterms.project.funder_nameSwedish Brain Powerfr
rioxxterms.project.funder_nameHjärnfondenfr
rioxxterms.project.funder_nameSwedish Parkinson Foundatinfr
bul.rights.periodeEmbargo6 moisfr
dc.audience.peerreviewOuifr
Collection:Articles publiés dans des revues avec comité de lecture

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