BACKGROUND Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease. METHODS Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague-Dawley rats prenatally challenged with polyriboinosinic-polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1β, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays. RESULTS Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood. CONCLUSIONS Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia.

中文翻译：

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Poly I：C处理的妊娠早期大鼠后代中神经炎症和前脉冲抑制的年龄相关变化。

背景技术妊娠期间的母体免疫激活（MIA）会增加成年后代精神分裂症的后期风险。据信神经炎症是该过程的基础。事后大脑研究发现精神分裂症患者的神经免疫系统发生了变化。然而，关于疾病过程中脑部炎症和行为的动态变化知之甚少。方法此处，在妊娠第9天对多核糖肌酸-多核糖基酸（Poly I：C）进行产前攻击的青春期和成年Sprague-Dawley大鼠进行了前脉冲抑制（PPI）测试，以确定早日接触Poly I触发的行为轨迹： C。在这两个年龄段的前额叶皮层（PFC）和海马（HC）中均确定了大脑的免疫变化。用免疫组织化学染色确定小胶质细胞和星形胶质细胞的状态。用酶联免疫吸附试验评估了两个大脑区域的IL-6，IL-1β和TNF-α的水平。结果精神分裂症的核心表型PPI中断仅在成年期出现。青春期和成年期的行为变化都伴随着小胶质细胞的活化（PFC和HC）。星形胶质细胞仅在PN60激活。在暴露于Poly I：C的母亲的后代中，促炎细胞因子（IL-1β，IL-6和TNF-α）的水平随大脑区域和时间的不同而不同，青春期期间的细胞因子水平要高于成年时期。结论我们的发现表明，在MIA大鼠的后代中，免疫激活出现在症状表现之前。我们得出的结论是，早期产前保利I：挑战C会导致与年龄有关的行为和神经炎症改变。这些数据为精神分裂症发展的神经炎症和神经病理机制提供了新的见解。他们还表明，青春期青春期在预防和治疗精神分裂症方面比成年更为重要。