Mattern Felix, Post Antonia, Solger Franziska, O'Leary Aet, Slattery David A, Reif Andreas, Haaf Thomas
Institute of Human Genetics, Julius-Maximilians-University, Würzburg, Germany.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
Behav Brain Res. 2019 Feb 1;359:143-148. doi: 10.1016/j.bbr.2018.10.037. Epub 2018 Oct 29.
To analyze the influences of early-life history on the brain epigenome, the offspring of mouse dams kept in an enriched or standard environment were exposed postnatally to enriched, standard, or adverse conditions. The methylation patterns of 7 candidate genes (9 loci) involved in developmental programming of stress vulnerability/resilience and psychiatric disease were analyzed in 6 brain regions of adult male and female mice. Exposure to an enriched prenatal environment was associated with widespread epigenetic changes (all of small effect size), affecting 29 of 324 (9%) gene/region-specific methylation patterns. The effects of either adverse or enriched postnatal conditions were tested separately in the two prenatal cohorts. Significant changes were observed in 2 of 324 (0.6%) loci in offspring of dams in a standard environment and 6 of 324 (1.9%) loci in animals that were exposed prenatally to an enriched environment. Prenatal life experiences appear to have a bigger effect on the adult brain epigenome than postnatal experiences. Positive prenatal life experiences may increase epigenetic plasticity of the brain later in life. All observed between-group differences were sex-specific, consistent with largely different developmental trajectories of the male and female brain. Multiple changes of small effect size are consistent with a multifactorial model of developmental programming of adult behavior and disease susceptibility.
为了分析早期生活经历对大脑表观基因组的影响，将饲养在丰富环境或标准环境中的母鼠后代在出生后暴露于丰富、标准或不良环境中。在成年雄性和雌性小鼠的6个脑区中，分析了7个参与应激易感性/恢复力和精神疾病发育编程的候选基因（9个位点）的甲基化模式。暴露于丰富的产前环境与广泛的表观遗传变化（所有效应大小均较小）相关，影响了324个基因/区域特异性甲基化模式中的29个（9%）。在两个产前队列中分别测试了不良或丰富的产后条件的影响。在标准环境中母鼠的后代中，324个位点中有2个（0.6%）观察到显著变化，在产前暴露于丰富环境的动物中，324个位点中有6个（1.9%）观察到显著变化。产前生活经历似乎比产后经历对成年大脑表观基因组的影响更大。积极的产前生活经历可能会增加大脑在生命后期的表观遗传可塑性。所有观察到的组间差异都是性别特异性的，这与雄性和雌性大脑在很大程度上不同的发育轨迹一致。多个小效应大小的变化与成年行为和疾病易感性发育编程的多因素模型一致。
