Tseng K Y, Roubert C, Do L, Rubinstein M, Kelly M A, Grandy D K, Low M J, Gershanik O S, Murer M G, Giros B, Raisman-Vozari R
Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Brain Res Mol Brain Res. 2000 Aug 14;80(1):1-6. doi: 10.1016/s0169-328x(00)00107-8.
The orphan nuclear receptor Nurr1 is critical for the survival of mesencephalic dopaminergic precursor neurons. Little is known about the mechanisms that regulate Nurr1 expression in vivo. Other members of this receptor family have been shown to be activated by dopamine. We sought to determine if Nurr1 expression is also regulated by endogenous dopamine through dopamine receptors. Consequently, we investigated the expression of Nurr1 mRNA in genetically modified mice lacking both functional copies of the D2 dopamine receptor gene and in their congenic siblings. Quantitative in situ hybridization demonstrated a significant increased expression of Nurr1 mRNA in the substantia nigra pars compacta and the ventral tegmental area of D2 dopamine receptor -/- mice. No change in Nurr1 expression was detected in other brain regions, such as the habenular nuclei and temporal cortex. Among the cell groups studied, mesencephalic dopaminergic neurons are unique in that they express both Nurr1 and the D2 dopamine receptor, and synthesize dopamine. Thus, it seems plausible that the selective increase in Nurr1 expression observed in D2 receptor-deficient mice is the consequence of an impaired dopamine autoreceptor function.
孤儿核受体Nurr1对中脑多巴胺能前体神经元的存活至关重要。关于体内调节Nurr1表达的机制知之甚少。该受体家族的其他成员已被证明可被多巴胺激活。我们试图确定Nurr1表达是否也受内源性多巴胺通过多巴胺受体的调节。因此，我们研究了缺乏D2多巴胺受体基因两个功能拷贝的基因改造小鼠及其同基因对照小鼠中Nurr1 mRNA的表达。定量原位杂交显示，D2多巴胺受体基因敲除小鼠黑质致密部和腹侧被盖区中Nurr1 mRNA的表达显著增加。在其他脑区，如缰核和颞叶皮质，未检测到Nurr1表达的变化。在所研究的细胞群中，中脑多巴胺能神经元的独特之处在于它们同时表达Nurr1和D2多巴胺受体，并合成多巴胺。因此，在D2受体缺陷小鼠中观察到的Nurr1表达选择性增加似乎是多巴胺自身受体功能受损的结果。
