Rapid increase of Nurr1 expression in the substantia nigra after 6-hydroxydopamine lesion in the striatum of the rat.

Abstract

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.