Nurr1 Is Required for Maintenance of Maturing and Adult Midbrain Dopamine Neurons
| Autor: | Kadkhodaei, B., Ito, T., Joodmardi, E., Mattsson, B., Rouillard, C., Carta, M., Muramatsu, S.-I., Sumi-Ichinose, C., Nomura, T., Metzger, D., Chambon, P., Lindqvist, E., Larsson, N.-G., Olson, L., Björklund, A., Ichinose, Hiroshi, Perlmann, T. |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Neurogenesis
Mice Transgenic Biology Midbrain Mice Dopamine Mesencephalon Pregnancy Nuclear Receptor Subfamily 4 Group A Member 2 medicine Animals Transcription factor Embryonic Stem Cells Dopamine transporter Neurons Integrases Pars compacta General Neuroscience Age Factors Gene targeting Articles Ventral tegmental area medicine.anatomical_structure nervous system Gene Targeting biology.protein Female Neuron Neuroscience medicine.drug |
| Popis: | 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 theNurr1gene have been identified in rare cases of disease; however, the significance of these observations remains unclear. Here, a mouse strain for conditional targeting of theNurr1gene was generated, andNurr1was 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.Nurr1deficiency 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 whenNurr1was 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. |
| Databáze: | OpenAIRE |
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