Abstract：
Epidemiological evidence has shown that maternal infection is a notable risk factor for developmental psychiatric disorders. Animal models have corroborated this link and demonstrated that maternal immune activation (MIA) induces long-term behavioural deficits and neuroimmunological responses to subsequent immune stress in offspring. However, it is unclear whether MIA offspring are more sensitive or more tolerant to immunological challenges from postnatal infections. Pregnant mice were weighed and injected with a single dose of polyinosinic-polycytidylic acid (poly I:C) or saline at gestational day 9.5, and their male offspring were exposed to poly I:C or saline again during adolescence, adulthood, and middle life. After a two-week recovery from the last exposure to poly I:C, the mice underwent behavioural and neuroendophenotypic evaluations. Finally, the mice were sacrificed, and the expression levels of inflammatory factors and the activation levels of glial cells in the cerebral cortex and hippocampus were evaluated. We found MIA mice have lifelong behavioural deficits and glial activation abnormalities. Postpartum infection exposure at different ages has different consequences. Adolescent and middle life exposure prevents sensorimotor gating deficiency, but adult exposure leads to increased sensitivity to MK-801. Moreover, MIA imposed a lasting impact on the neuroimmune profile, resulting in an enhanced cytokine-associated response and diminished microglial reactivity to postnatal infection. Our results reveal an intricate interplay between prenatal and postpartum infection in neuropsychiatric phenotypes, which identify potential windows where preventive or mitigating measures could be applied.
摘要：
流行病学证据表明，母体感染是发育性精神疾病的显着危险因素。动物模型已经证实了这一联系，并证明母体免疫激活（MIA）诱导后代对随后的免疫应激的长期行为缺陷和神经免疫反应。然而,目前尚不清楚MIA后代对出生后感染的免疫挑战是否更敏感或更耐受.在妊娠第9.5天对妊娠小鼠称重并注射单剂量的聚肌苷酸-聚胞嘧啶酸（聚I：C）或生理盐水，并在青春期将其雄性后代再次暴露于聚I：C或生理盐水，成年,和中间生活。在从最后一次接触聚I:C后恢复了两周，对小鼠进行了行为和神经内表型评估.最后,小鼠被处死，并评估大脑皮质和海马中炎性因子的表达水平和胶质细胞的活化水平。我们发现MIA小鼠具有终生的行为缺陷和神经胶质激活异常。不同年龄的产后感染暴露有不同的后果。青少年和中年暴露可防止感觉运动门控缺陷，但是成人暴露会导致对MK-801的敏感性增加。此外，MIA对神经免疫谱产生了持久的影响，导致细胞因子相关反应增强，小胶质细胞对出生后感染的反应性降低。我们的结果揭示了神经精神表型的产前和产后感染之间的复杂相互作用，确定可以应用预防或缓解措施的潜在窗口。
