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首页> 外文期刊>The European Journal of Neuroscience >Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor.
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Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor.

机译：Fischer 344大鼠对反复应激的脆弱性的表征：可能参与了microRNA介导的糖皮质激素受体下调。

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In the present study, we established and characterized an animal model of vulnerability to repeated stress. We found that control Sprague-Dawley (SD) rats showed a gradual decrease in the HPA axis response following 14 days of repeated restraint stress, whereas Fischer 344 (F344) rats did not show such HPA axis habituation. Similar habituation was observed in the expression of c-fos mRNA, corticotropin-releasing hormone hnRNA, and phospho-CREB and phospho-ERK proteins in the hypothalamic paraventricular nucleus (PVN) of SD rats, but not in the F344 rats. In addition, repeatedly restrained F344 rats exhibited decreased cell proliferation in the dentate gyrus of the hippocampus and increased anxiety-related behaviours, while repeatedly restrained SD rats exhibited a selective enhancement of hippocampal cell proliferation in the ventral area. Moreover, we found a lower expression of glucocorticoid receptor (GR) protein, but not mRNA, in the PVN of F344 rats compared to SD rats. We also identified that microRNA (miR)-18a inhibited translation of GR mRNA in cultured neuronal cells and that increased expression of miR-18a in the PVN was observed in F344 rats compared with SD rats. These strain differences in GR protein levels were not found in the hippocampus and prefrontal cortex, and the expression of miR-18a was much lower in these brain regions than in the PVN. Our results suggest that F344 rats could be a useful animal model for studying vulnerability to repeated stress, and that miR-18a-mediated down-regulation of GR translation may be an important factor to be considered in susceptibility to stress-related disorders.
机译：在本研究中，我们建立并表征了易受反复胁迫的动物模型。我们发现，对照Sprague-Dawley（SD）大鼠在反复施加约束力14天后显示HPA轴反应逐渐降低，而Fischer 344（F344）大鼠未显示此类HPA轴适应。在SD大鼠的下丘脑室旁核（PVN）中观察到c-fos mRNA，促肾上腺皮质激素释放激素hnRNA以及磷酸化CREB和磷酸化ERK蛋白的表达，但在F344大鼠中没有类似的习惯。此外，反复受约束的F344大鼠在海马齿状回中的细胞增殖减少，并且与焦虑相关的行为增加，而反复受约束的SD大鼠在腹侧区域的海马细胞增殖选择性增强。此外，我们发现与SD大鼠相比，F344大鼠的PVN中糖皮质激素受体（GR）蛋白的表达较低，而mRNA没有。我们还发现，与SD大鼠相比，在F344大鼠中观察到microRNA（miR）-18a抑制了培养的神经元细胞中GR mRNA的翻译，并且在PVN中观察到miR-18a表达的增加。在海马和前额叶皮层中未发现GR蛋白水平的这些差异，并且在这些大脑区域中miR-18a的表达远低于PVN。我们的研究结果表明F344大鼠可能是有用的动物模型，用于研究易受重复应激的影响，而miR-18a介导的GR翻译下调可能是考虑与应激相关疾病易感性的重要因素。

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