Abstract：
Epidemiological and experimental evidence demonstrates that maternal exposure to infection during gestation increases the offspring\'s risk of developing schizophrenia and other neurodevelopmental disorders. In addition, the NRG-ErbB4 signaling pathway is involved in brain development and neuropsychiatric disorders. Specifically, this pathway modulates the dopaminergic and GABAergic systems and is expressed in the early stages of prenatal development. We recently demonstrated that maternal immune activation (MIA) at late gestation altered the expression of NRG1, its receptor ErbB4, and the dopamine D2 receptor four hours post-injection of viral or LPS in the fetal brain. We also reported that blocking the ErbB pathway during adolescence resulted in increased striatal DA content and reduced preference for sweetness and alcohol that persists into adulthood. However, the combined effects of MIA, re-activation of the immune system, and disruption of the ErbB signaling during adolescence would affect young adult mice\'s behavioral phenotype is unknown. Here, we report that the expression levels of the NRG1, ErbB4, GAD67, and BDNF were changed as responses to MIA and blocked the ErbB signaling in the frontal cortex of adolescent mice. MIA-Offspring during late gestation and immune system re-activation during adolescence spent less time in the open arms of the elevated plus-maze in adulthood. At the same time, MIA-offspring administrated with the pan-ErbB inhibitor during adolescence spent the same amount of time in the opened arm as the control mice. Combining the ErbB signaling disruption during adolescence leads to a social interaction impairment in female offspring, but not male, without affecting the offspring\'s motor activity, long-term recognition, and working memory. These results imply that blocking the ErbB signaling during adolescence prevents the development of anxiety-like behavior of the MIA offspring later in life and suggest that this interaction does not reduce the risk of female MIA offspring developing impaired social behavior.
摘要：
流行病学和实验证据表明，孕妇在妊娠期间接触感染会增加后代患精神分裂症和其他神经发育障碍的风险。此外,NRG-ErbB4信号通路参与脑发育和神经精神疾病.具体来说,该途径调节多巴胺能和GABA能系统，并在产前发育的早期阶段表达。我们最近证明，妊娠晚期的母体免疫激活（MIA）在胎儿脑中注射病毒或LPS后四小时改变了NRG1，其受体ErbB4和多巴胺D2受体的表达。我们还报告说，在青春期阻断ErbB途径会导致纹状体DA含量增加，并降低对甜味和酒精的偏好，这种偏好会持续到成年期。然而,MIA的综合影响,重新激活免疫系统,和破坏的ErbB信号在青春期会影响年轻的成年小鼠的行为表型是未知的。这里,我们报道,NRG1,ErbB4,GAD67和BDNF的表达水平随着对MIA的反应而改变,并阻断了青春期小鼠额叶皮质中的ErbB信号传导.MIA-后代在妊娠后期和青春期免疫系统的重新激活中在成年期高架迷宫的张开双臂中花费的时间较少。同时,在青春期期间施用pan-ErbB抑制剂的MIA后代在张开的手臂中花费的时间与对照小鼠相同。在青春期结合ErbB信号中断会导致女性后代的社交互动受损，但不是男性,不影响后代的运动活动，长期认可,和工作记忆。这些结果表明，在青春期阻断ErbB信号可以防止MIA后代在以后的生活中发生焦虑样行为，并且表明这种相互作用并不能降低女性MIA后代发生受损社会行为的风险。
