Ojeda Viviana, Fuentealba José Antonio, Galleguillos Danny, Andrés María Estela
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
J Neurosci Res. 2003 Sep 1;73(5):686-97. doi: 10.1002/jnr.10705.
Nurr1 is a transcription factor essential for the genesis of ventral dopaminergic neurons. In this study, we investigated the expression of Nurr1 protein and mRNA in the adult rat brain by using immunohistochemistry and in situ hybridization, respectively. Another aim of our study was to investigate Nurr1 expression in substantia nigra after dopamine depletion induced by the injection of 6-hydroxydopamine in the striatum. We observed that Nurr1 mRNA and protein are expressed in several brain regions, including cortex, hippocampus, substantia nigra, and ventral tegmental area, in agreement with previous reports using in situ hybridization. Additionally, we found that Nurr1 is expressed in brain regions that have not been previously reported, such as striatum, septum, and superior colliculus. Highest levels of expression were found in cortex, medial septum, dentate gyrus, some hypothalamic nuclei, and substantia nigra. Interestingly, we observed that, in the superior colliculus, Nurr1 protein is localized in the cytoplasm of cells, whereas, in other regions, it was localized mainly in the nuclei, suggesting that Nurr1 subcellular localization is regulated and may have functional implications. Dopamine depletion induced by an injection of 6-hydroxydopamine into the striatum produced an increase in the number of cells expressing Nurr1 mRNA and protein in both substantia nigra compacta and substantia nigra reticulata, ipsilateral and contralateral to the lesioned side, measured 24 hr after the 6-hydroxydopamine injection. These results suggest that Nurr1 may be involved in many neuronal functions in the adult central nervous system and, in particular, might be related to the compensation processes that take place in dopaminergic cells in order to normalize extracellular dopamine levels in the striatum.
Nurr1是腹侧多巴胺能神经元生成所必需的转录因子。在本研究中，我们分别使用免疫组织化学和原位杂交技术，研究了成年大鼠脑中Nurr1蛋白和mRNA的表达情况。我们研究的另一个目的是，探究在纹状体注射6-羟基多巴胺诱导多巴胺耗竭后，黑质中Nurr1的表达情况。我们观察到，与先前使用原位杂交的报道一致，Nurr1 mRNA和蛋白在包括皮层、海马体、黑质和腹侧被盖区在内的多个脑区中表达。此外，我们发现Nurr1在先前未报道的脑区中表达，如纹状体、隔区和上丘。在皮层、内侧隔区、齿状回、一些下丘脑核团和黑质中发现了最高水平的表达。有趣的是，我们观察到，在上丘中，Nurr1蛋白定位于细胞的细胞质中，而在其他区域，它主要定位于细胞核中，这表明Nurr1的亚细胞定位受到调控，可能具有功能意义。在纹状体注射6-羟基多巴胺诱导多巴胺耗竭后，在6-羟基多巴胺注射24小时后测量发现，在损伤侧同侧和对侧的黑质致密部和黑质网状部中，表达Nurr1 mRNA和蛋白的细胞数量均增加。这些结果表明，Nurr1可能参与成年中枢神经系统中的许多神经元功能，特别是可能与多巴胺能细胞中发生的补偿过程有关，以便使纹状体中的细胞外多巴胺水平正常化。
