Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back.
Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back.
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DOI：
10.1038/s41380-018-0274-3
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发表时间：
2020-03
影响因子：
11
通讯作者：
McEwen BS
中科院分区：
文献类型：
--
作者：
Marrocco J;Einhorn NR;Petty GH;Li H;Dubey N;Hoffman J;Berman KF;Goldman D;Lee FS;Schmidt PJ;McEwen BS
Premenstrual dysphoric disorder (PMDD) affects over 5% of women, with symptoms similar to anxiety and major depression, and is associated with differential sensitivity to circulating ovarian hormones. Little is known about the genetic and epigenetic factors that increase the risk to develop PMDD. We report that 17β-estradiol (E2) affects the behavior and the epigenome in a mouse model carrying a single-nucleotide polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met), in a way that recapitulates the hallmarks of PMDD. Ovariectomized mice heterozygous for the BDNF Met allele (Het-Met) and their matched wild-type (WT) mice were administered estradiol or vehicle in drinking water for 6 weeks. Using the open field and the splash test, we show that E2 add-back induces anxiety-like and depression-like behavior in Het-Met mice, but not in WT mice. RNA-seq of the ventral hippocampus (vHpc) highlights that E2-dependent gene expression is markedly different between WT mice and Het-Met mice. Through a comparative whole-genome RNA-seq analysis between mouse vHpc and lymphoblastoid cell line cultures from control women and women with PMDD, we discovered common epigenetic biomarkers that transcend species and cell types. Those genes include epigenetic modifiers of the ESC/E(Z) complex, an effector of response to ovarian steroids. Although the BDNF Met genotype intersects the behavioral and transcriptional traits of women with PMDD, we suggest that these similarities speak to the epigenetic factors by which ovarian steroids produce negative behavioral effects.
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DOI：
10.1093/ijnp/pyx078
发表时间：
2017-12-01
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Miyamoto Y;Iegaki N;Fu K;Ishikawa Y;Sumi K;Azuma S;Uno K;Muramatsu SI;Nitta A
通讯作者：
Nitta A
影响因子：
10.6
作者：
Bath, Kevin G.;Chuang, Jocelyn;Spencer-Segal, Joanna L.;Amso, Dima;Altemus, Margaret;McEwen, Bruce S.;Lee, Francis S.
通讯作者：
Lee, Francis S.
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
56.9
作者：
Kasinath, Vignesh;Faini, Marco;Nogales, Eva
通讯作者：
Nogales, Eva
影响因子：
--
作者：
Hewetson, Aveline;Chilton, Beverly S.
通讯作者：
Chilton, Beverly S.