Altpere A, Raud S, Sütt S, Reimets R, Visnapuu T, Toots M, Vasar E
Institute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre of Excellence in Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Institute of Biomedicine and Translational Medicine, Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre of Excellence in Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Behav Brain Res. 2018 Oct 15;352:94-98. doi: 10.1016/j.bbr.2017.09.039. Epub 2017 Sep 28.
In this work, the effect of mild stress (elevated plus maze test, EPM) on the expression of endoplasmic reticulum (ER) stress markers in different brain areas of wild type (WT) and Wfs1-deficient (Wfs1KO) mice was investigated. The following ER stress markers were studied: activating transcription factor 6α (Atf6α), protein kinase-like ER kinase (Perk), X-box binding protein 1 (Xbp1) and its spliced form (Xbp1s), 78-kilodalton glucose regulated protein (Grp78), 94-kilodalton glucose regulated protein (Grp94), C/EBP homologous protein (Chop). Wfs1KO and WT mice, not exposed to EPM, had similar patterns of ER stress markers in the studied brain areas. The exploratory activity of Wfs1KO mice in the EPM was inhibited compared to WT mice, probably reflecting increased anxiety in genetically modified mice. In response to the EPM, activation of inositol-requiring transmembrane kinase and endonuclease 1α (Ire1α) ER stress pathway was seen in both genotypes, but in different brain areas. Such a brain region-specific Ire1α activation was linked with dominant behavioural trends in these mice as more anxious, neophobic Wfs1KO mice had increased ER stress markers expression in the temporal lobe, the brain region related to anxiety, and more curious WT mice had ER stress markers increased in the ventral striatum which is related to the exploratory drive. The molecular mechanism triggering respective changes in ER stress markers in these brain regions is likely related to altered levels of monoamine neurotransmitters (serotonin, dopamine) in Wfs1KO mice.
在本研究中，我们探究了轻度应激（高架十字迷宫试验，EPM）对野生型（WT）和Wfs1基因缺陷型（Wfs1KO）小鼠不同脑区内质网（ER）应激标志物表达的影响。我们研究了以下ER应激标志物：激活转录因子6α（Atf6α）、蛋白激酶样内质网激酶（Perk）、X盒结合蛋白1（Xbp1）及其剪接形式（Xbp1s）、78千道尔顿葡萄糖调节蛋白（Grp78）、94千道尔顿葡萄糖调节蛋白（Grp94）、C/EBP同源蛋白（Chop）。未暴露于EPM的Wfs1KO和WT小鼠在研究的脑区中具有相似的ER应激标志物模式。与WT小鼠相比，Wfs1KO小鼠在EPM中的探索活动受到抑制，这可能反映了基因改造小鼠焦虑情绪的增加。对EPM的反应中，两种基因型在不同脑区均出现了肌醇需求跨膜激酶和核酸内切酶1α（Ire1α）ER应激途径的激活。这种脑区特异性的Ire1α激活与这些小鼠的主要行为趋势相关，因为更焦虑、有新物恐惧症的Wfs1KO小鼠在与焦虑相关的颞叶中ER应激标志物表达增加，而更具好奇心的WT小鼠在与探索驱动力相关的腹侧纹状体中ER应激标志物增加。触发这些脑区ER应激标志物各自变化的分子机制可能与Wfs1KO小鼠中单胺类神经递质（血清素、多巴胺）水平的改变有关。
