A measure of glucocorticoid load provided by DNA methylation of Fkbp5 in mice.
A measure of glucocorticoid load provided by DNA methylation of Fkbp5 in mice.
复制标题
DOI：
10.1007/s00213-011-2307-3
复制
发表时间：
2011-11
影响因子：
3.4
通讯作者：
Wand, Gary S.
中科院分区：
文献类型：
--
作者：
Lee, Richard S.;Tamashiro, Kellie L. K.;Yang, Xiaoju;Purcell, Ryan H.;Huo, Yuqing;Rongione, Michael;Potash, James B.;Wand, Gary S.
考虑到皮质醇失调对神经精神和代谢紊乱的影响，能够准确地计算糖皮质激素负荷是很重要的，糖皮质激素负荷是一种衡量不平衡负荷的指标。计算皮质醇负荷的一个主要问题是，现有的测量方法反映的是短期内的皮质醇暴露，还没有被证明能够可靠地量化几周或几个月的皮质醇负荷。我们用饮用水中的皮质酮处理了两组小鼠，并确定了连续4周的血浆皮质酮水平与治疗结束时测定的特定糖皮质激素敏感基因FKBP5的全血DNA甲基化(DNaM)变化的关系。我们观察到，从一次抽血中测定的FKBP5内含子1区域dNaM减少的百分比强烈地反映了在糖皮质激素暴露的前一个月每周产生的平均糖皮质激素负荷。DNaM与糖皮质激素诱导的脾重量和内脏脂肪的终末器官改变也有很强的相关性。我们在高架加迷宫中测试了这些动物的一部分类似焦虑的行为，发现血液中的dNaM在确定糖皮质激素暴露的行为后果方面也具有预测价值。FKBP5基因甲基化的全血评估是一个整合了4周糖皮质激素暴露的生物标记物，在过度暴露状态下可能是一个有用的衡量标准。在慢性社会压力期间，确定FKBP5 dNaM的变化是否也可以作为糖皮质激素负荷的生物标志物是很重要的。
Given the contribution of cortisol dysregulation to neuropsychiatric and metabolic disorders, it is important to be able to accurately compute glucocorticoid burden, a measure of allostatic load. One major problem in calculating cortisol burden is that existing measures reflect cortisol exposure over a short duration and have not been proven to reliably quantify cortisol burden over weeks or months. We treated two cohorts of mice with corticosterone in the drinking water and determined the relationship between serial plasma corticosterone levels drawn over 4 weeks and the whole-blood DNA methylation (DNAm) changes in a specific glucocorticoid-sensitive gene, Fkbp5, determined at the end of the treatment period. We observed that the percent reduction in DNAm in the intron 1 region of Fkbp5 determined from a single blood draw strongly reflected average glucocorticoid burden generated weekly during the prior month of glucocorticoid exposure. There were also strong correlations in DNAm with glucocorticoid-induced end organ changes in spleen weight and visceral fat. We tested a subset of these animals for anxiety-like behavior in the elevated plus maze and found that DNAm in the blood also has predictive value in determining the behavioral consequences of glucocorticoid exposure. A whole-blood assessment of Fkbp5 gene methylation is a biomarker that integrates 4 weeks of glucocorticoid exposure and may be a useful measure in states of excess exposure. It will be important to determine if Fkbp5 DNAm changes can also be a biomarker of glucocorticoid burden during chronic social stress.
登录
查看更多内容
影响因子：
5
作者：
Hansen, ÅM;Garde, AH;Christensen, JM
通讯作者：
Christensen, JM
影响因子：
3.2
作者：
Kelly, WF;Kelly, MJ;Faragher, B
通讯作者：
Faragher, B
影响因子：
2.7
作者：
Colella, S;Shen, L;Krahe, R
通讯作者：
Krahe, R
影响因子：
9.8
作者：
McEwen, BS
通讯作者：
McEwen, BS
影响因子：
5.3
作者：
SAPOLSKY, RM;UNO, H;FINCH, CE
通讯作者：
FINCH, CE