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

Auteur(s): Kadkhodaei, Banafsheh; Ito, Takehito; Joodmardi, Eliza; Mattsson, Bengt; Rouillard, Claude; Carta, Manolo; Muramatsu, Shin-Ichi; Sumi-Ichinose, Chiho; Nomura, Takahide; Metzger, Daniel; Chambon, Pierre; Lindqvist, Eva; Larsson, Nils-Göran; Olson, Lars; Björklund, Anders; Ichinose, Hiroshi; Perlmann, Thomas
Résumé: Transcription 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.
Type de document: Article de recherche
Date de publication: 16 décembre 2009
Date de la mise en libre accès: 12 février 2018
Version du document: VoR
Lien permanent: http://hdl.handle.net/20.500.11794/17001
Ce document a été publié dans: The Journal of neuroscience, Vol. 29 (50), 15923-15932 (2009)
http://dx.doi.org/10.1523/JNEUROSCI.3910-09.2009
Society for Neuroscience
Autre version disponible: 10.1523/JNEUROSCI.3910-09.2009
20016108
Collection :Articles publiés dans des revues avec comité de lecture

Fichier(s) :
Description TailleFormat 
nurr1.pdf8.19 MBAdobe PDFMiniature
Télécharger
Tous les documents dans CorpusUL sont protégés par la Loi sur le droit d'auteur du Canada.