Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Neurosci Res. 2010 Aug 1;88(10):2284-93. doi: 10.1002/jnr.22377.
The immediate-early gene Nurr1 is a member of the inducible orphan nuclear receptor family. Nurr1 is essential to the differentiation, maturation, and maintenance of midbrain dopaminergic neurons and is expressed in different brain regions. We have reported that adult mice with reduced Nurr1 expression displayed an increase in immobility response to acute stress. These mice were also deficient in the retention of emotional memory. Thus, Nurr1 expression seems to be relevant to normal cognitive processes. To investigate the response of Nurr1 to a stress stimulus, Nurr1 mRNA expression was examined by in situ hybridization in adult mice using a depression-like behavior paradigm, the forced swim test. The Nurr1 gene was rapidly and widely up-regulated throughout the brain, including cortical areas (i.e., prefrontal cortex, primary and secondary visual cortex, primary auditory cortex, and secondary somatosensory cortex), hippocampus (dentate gyrus, CA1, CA2, and CA3), and midbrain (substantia nigra pars compacta and ventral tegmental area) at 30 min and 3 hr after the forced swim test. Dopamine content was reduced in prefrontal cortex and midbrain following swim stress. These results suggest that the increase in Nurr1 expression might be a compensatory mechanism to counteract the changes in forebrain dopamine transmission in coping with acute stress.
立即早期基因 Nurr1 是诱导孤儿核受体家族的成员。Nurr1 对中脑多巴胺能神经元的分化、成熟和维持至关重要，并在不同的脑区表达。我们已经报道，表达减少 Nurr1 的成年小鼠对急性应激的不动反应增加。这些小鼠在情绪记忆的保留方面也存在缺陷。因此，Nurr1 的表达似乎与正常认知过程有关。为了研究 Nurr1 对应激刺激的反应，我们使用抑郁样行为范式，强迫游泳试验，通过原位杂交在成年小鼠中检查 Nurr1 mRNA 的表达。在强迫游泳试验 30 分钟和 3 小时后，Nurr1 基因在大脑的广泛区域（如前额叶皮层、初级和次级视觉皮层、初级听觉皮层和次级躯体感觉皮层）、海马（齿状回、CA1、CA2 和 CA3）和中脑（黑质致密部和腹侧被盖区）中迅速上调。游泳应激后，前额叶皮层和中脑的多巴胺含量减少。这些结果表明，Nurr1 表达的增加可能是一种代偿机制，以抵消应对急性应激时前脑多巴胺传递变化。
