The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology
The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology
复制标题
DOI：
10.1523/jneurosci.0099-06.2006
复制
发表时间：
2006-05-03
影响因子：
5.3
通讯作者：
Feldon, J
中科院分区：
文献类型：
--
作者：
Meyer, U;Nyffeler, M;Feldon, J
对早期大脑发育的干扰与几种神经精神障碍有关，包括自闭症、精神分裂症和精神发育迟滞。流行病学研究表明，发生这些疾病的风险增加了产前母体感染，可能是由于神经发育缺陷引发的尼古丁相关的炎症事件。在这里，我们证明了在小鼠妊娠中期和晚期之间的母体免疫挑战的影响是分离的胎儿脑细胞因子对母体炎症的反应和大脑和行为的病理后果。具体而言，促炎和抗炎细胞因子在胎儿大脑中的相对表达，以响应母亲的免疫挑战可能是一个重要的决定因素，在其他发展因素中出现的精确的病理档案在以后的生活。因此，中期和晚期妊娠期对应于两个窗口，具有不同的脆弱性成人行为功能障碍，脑神经病理学在青春期早期，和急性细胞因子反应在胎儿大脑。
Disturbance to early brain development is implicated in several neuropsychiatric disorders including autism, schizophrenia, and mental retardation. Epidemiological studies have indicated that the risk of developing these disorders is enhanced by prenatal maternal infection, presumably as a result of neurodevelopmental defects triggered by cytokine-related inflammatory events. Here, we demonstrate that the effects of maternal immune challenge between middle and late gestation periods in mice are dissociable in terms of fetal brain cytokine responses to maternal inflammation and the pathological consequences in brain and behavior. Specifically, the relative expression of pro- and anti-inflammatory cytokines in the fetal brains in response to maternal immune challenge may be an important determinant among other developmental factors for the precise pathological profile emerging in later life. Thus, the middle and late gestation periods correspond to two windows with differing vulnerability to adult behavioral dysfunction, brain neuropathology in early adolescence, and of the acute cytokine responses in the fetal brain.