Non-genetic programming of adult emotional behavior by the grandmother

祖母对成人情绪行为的非遗传编程

• 批准号: 8837695
• 负责人: Miklos Toth
• 金额: $ 21.19万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-14 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837695
• 关键词: Adult; Adult Children; Adverse effects; Affect; Animal Model; Anxiety; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Behavioral; Brain; Cells; Characteristics; Child; Chronic stress; Cytokine Signaling; Cytoplasm; DNA Methylation; Data; Daughter; Development; Disease; Embryo; Embryo Transfer; Environment; Epigenetic Process; Event; Exhibits; Exposure to; Female; Generations; Genes; Genetic; Genetic Programming; Genome; Germ; Germ Cells; Gonadal structure; Health; Heritability; Hippocampus (Brain); Hormonal; Hormones; Human; Incidence; Infection; Laboratories; Malnutrition; Mammals; Maternal Exposure; Mediating; Mental Depression; Methylation; Mothers; Mus; Mutation; Neurons; Nutrient; Phenotype; Population; Pregnancy; Reporting; Risk; Route; Schizophrenia; Serotonin Receptor 5-HT1A; Signal Pathway; Somatic Cell; Specific qualifier value; Stress; Synapses; Testing; Time; To specify; base; behavioral study; egg; embryo cell; emotional behavior; genetic variant; grandchild; interest; intergenerational; neuropsychiatry; non-genetic; offspring; prenatal exposure; programs; receptor; research study; social; transmission process

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.

描述（由申请人提供）：在人类和动物模型中，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)失活对小鼠妊娠期的影响，表现为后代的焦虑和应激反应增强。这些母性条件的后果通常并不局限于第一代，而且实际上已经发现会改变孙辈的行为。我们最近的数据表明，母亲5-HT1AR缺陷的焦虑诱导效应延伸到F2代（孙子）。虽然这种行为的代际非基因“遗传”增加了人群中神经精神疾病的发病率，但其发生的潜在机制基本上是未知的。通过胚胎移植和全基因组表观遗传分析，研究了不良妊娠环境对行为和表观遗传的影响是如何传递给连续两代后代的。