BDNF Val66Met基因型与雌二醇反向添加的跨物种模型中的经前焦虑障碍转录组的表观遗传相交

Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back

BDNF：脑源性神经营养因子

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 an