Non-genetic programming of adult emotional behavior by the grandmother

描述(申请人提供)：母亲营养不良、感染、压力，甚至突变都会扰乱妊娠环境，导致后代在人类和动物模型中出现行为异常的风险增加。我们报道了母体5-HT1A受体(R)失活对小鼠的妊娠影响，表现为焦虑和子代的应激反应增加。这些母性疾病的后果往往不仅限于第一代，而且实际上已经被发现改变了孙辈的行为。我们最近的数据显示，母体5-HT1AR缺陷的焦虑诱导效应延伸到F2代(孙辈)。虽然这种代际行为的非遗传“遗传”增加了人群中神经精神疾病的发生率，但其发生的潜在机制基本上是未知的。利用胚胎移植和全基因组表观遗传学分析，我们研究了不良妊娠环境的行为和表观遗传效应如何传播到连续的两代后代。

DESCRIPTION (provided by applicant): Maternal malnutrition, infection, stress, and even mutations can perturb the gestational environment, resulting in increased risk for offspring to develop behavioral abnormalities in both human and animal models. We reported the gestational effect of the inactivation of the maternal 5-HT1A receptor (R) in mice, manifested as anxiety and increased stress responsiveness in the offspring. The consequences of these maternal conditions are often not limited to the first generation, and have actually been found to alter the behavior of the grandchildren. Our recent data show that the anxiety-inducing effect of maternal 5-HT1AR deficit is extended to the F2 generation (grandchildren). Although such intergenerational non-genetic "inheritance" of behavior increases the incidence of neuropsychiatric disease in the population, the underlying mechanism by which this occurs is essentially unknown. Using embryo transfer and whole genome epigenetic analysis, we study how the behavioral and epigenetic effects of adverse gestational environment propagate to two consecutive generations of offspring.