Iterative somatic epigenetic programming of behavior across multiple generations

点击翻译按钮获取中文摘要

Abstract Inheritance is typically associated with the Mendelian transmission of information from parents to offspring by alleles, but empirical data clearly suggest that traits can be acquired from ancestors by mechanisms that do not involve DNA sequence. Information that is non-genetically transmitted includes parental experience, exposure to environmental chemicals, drugs of abuse, and parental mutations and polymorphisms that change the parental environment. Non-genetic inheritance has been observed for a wide range of diseases, including psychiatric disorders. Non-genetic inheritance is not limited to the first generation of the progeny, but can involve the grandchildren and even further generations. While multigenerational transmission of traits is typically believed to be gametic, we previously showed that it can occur iteratively through a somatic mechanism during gestation. We refer to this mode of transmission of behavioral traits as iterative somatic programming. We recently found that multigenerational non-genetic transmission of anxiety and stress traits is associated and perhaps caused by maternal autoimmunity perpetuating from one generation to the next. We hypothesize that maternal autoreactive antibodies cross the placenta and cause inflammation in the offspring, manifesting as anxiety in adulthood. This hypothesis will be tested by interrupting the cycle of iterative programming of offspring anxiety, by mitigating the maternal autoimmunity and/or interfering with the transfer of the maternal autoantibodies to the fetus by various immunological approaches. This mechanistic work may help explain the increased incidence of autism and neuropsychiatric conditions in children of mothers with autoimmune diseases. Taken together, our experiments test a novel mechanism that may contribute to the iterative somatic transmission of pathological behavioral traits, particularly those associated with maternal autoimmunity. In contrast to genetic, somatic inheritance of traits is not inevitable, and therefore could be prevented, once the underlying mechanism is better understood.