Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure.
Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure.
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DOI：
10.1016/j.psyneuen.2014.03.003
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发表时间：
2014-06
影响因子：
3.7
通讯作者：
Lee, Richard S.
中科院分区：
文献类型：
--
作者：
Ewald, Erin R.;Wand, Gary S.;Seifuddin, Fayaz;Yang, Xiaoju;Tamashiro, Kellie L.;Potash, James B.;Zandi, Peter;Lee, Richard S.
利用外周组织来鉴定神经精神疾病的分子底物的表观遗传学研究依赖于这样的假设，即在大脑中发生的疾病相关的细胞改变在外周组织（如血液）中被反映和检测。我们试图通过使用库欣氏病的小鼠模型来验证这一假设，并询问糖皮质激素诱导的表观遗传变化是否与这些组织类型相关。在饮用水中加入不同剂量的糖皮质激素，对小鼠进行为期四周的治疗，以评估应激反应基因Fkbp5的基因表达和DNA甲基化（DNAm）变化。血液（R2 = 0.68，P = 7.1×10−10）和大脑（R2 = 0.33，P = 0.001）的DNAm和四周平均血浆皮质酮水平之间观察到显著的线性关系。此外，血液中的甲基化程度变化与海马中的甲基化（R2 = 0.49，P = 2.7×10−5）和表达（R2 = 0.43，P = 3.5×10−5）变化显著相关，值得注意的是，甲基化变化发生在血液和脑组织之间的不同内含子区域。虽然我们的发现仅限于单个基因中的几个内含子CpG，但我们的结果表明，来自血液的DNA可用于评估大脑中发生的糖皮质激素诱导的动态变化。然而，这种相关性分析是有效的，这些表观遗传变化的组织特异性的位置可能需要考虑时，调查脑相关的外周组织的变化。
Epigenetic studies that utilize peripheral tissues to identify molecular substrates of neuropsychiatric disorders rely on the assumption that disease-relevant, cellular alterations that occur in the brain are mirrored and detectable in peripheral tissues such as blood. We sought to test this assumption by using a mouse model of Cushing’s disease and asking whether epigenetic changes induced by glucocorticoids can be correlated between these tissue types. Mice were treated with different doses of glucocorticoids in their drinking water for four weeks to assess gene expression and DNA methylation (DNAm) changes in the stress response gene Fkbp5. Significant linear relationships were observed between DNAm and four-week mean plasma corticosterone levels for both blood (R2 = 0.68, P = 7.1×10−10) and brain (R2 = 0.33, P = 0.001). Further, degree of methylation change in blood correlated significantly with both methylation (R2 = 0.49, P = 2.7×10−5) and expression (R2 = 0.43, P = 3.5×10−5) changes in hippocampus, with the notable observation that methylation changes occurred at different intronic regions between blood and brain tissues. Although our findings are limited to several intronic CpGs in a single gene, our results demonstrate that DNA from blood can be used to assess dynamic, glucocorticoid-induced changes occurring in the brain. However, for such correlation analyses to be effective, tissue-specific locations of these epigenetic changes may need to be considered when investigating brain-relevant changes in peripheral tissues.
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影响因子：
3.4
作者：
Lee, Richard S.;Tamashiro, Kellie L. K.;Yang, Xiaoju;Purcell, Ryan H.;Huo, Yuqing;Rongione, Michael;Potash, James B.;Wand, Gary S.
通讯作者：
Wand, Gary S.
影响因子：
2.7
作者：
Colella, S;Shen, L;Krahe, R
通讯作者：
Krahe, R
影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
30.8
作者：
Binder, EB;Salyakina, D;Muller-Myhsok, B
通讯作者：
Muller-Myhsok, B
DOI：
10.1007/978-1-61779-848-1_21
发表时间：
2012
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Hackler, Laszlo Jr;Masuda, Tomohiro;Oliver, Verity F;Merbs, Shannath L;Zack, Donald J
通讯作者：
Zack, Donald J