Prenatal immune challenge compromises development of upper-layer but not deeper-layer neurons of the mouse cerebral cortex
Prenatal immune challenge compromises development of upper-layer but not deeper-layer neurons of the mouse cerebral cortex
复制标题
产前免疫挑战会损害小鼠大脑皮层上层神经元的发育，但不会损害深层神经元的发育
DOI：
10.1002/jnr.22636
复制
发表时间：
2011
期刊：
影响因子：
4.2
通讯作者：
Furukawa S
中科院分区：
文献类型：
--
作者：
Soumiya H;Fukumitsu H;Furukawa S
母亲在怀孕期间感染是后代发展严重的大脑疾病，包括精神分裂症的环境风险因素。然而，人们对产前感染与以后生活中出现认知和行为功能障碍之间联系的神经发育机制知之甚少。通过将病毒模拟物聚核糖肌苷-聚核糖胞苷酸（Poly I：C）注射到小鼠体内，我们研究了妊娠期间母体免疫攻击对大脑皮层发育的影响，大脑皮层是认知的反应器官。母体免疫系统的刺激并不影响出生后10天和8周大的后代的皮质神经元的细胞数量或密度，而上层特异性转录因子的基因表达显著降低，而不影响深层的基因表达。此外，产前Poly I：C注射在后期损害了上层神经元的突触发育，并且在出生后8周龄的后代中，神经元细胞体周围的突触素和谷氨酸脱羧酶67阳性斑点减少，树突棘密度增加。考虑到它们对认知功能的重要性，上层神经元表型发育的特定异常可能是子宫内暴露于感染后出现的精神脑和行为功能障碍的发展的基础。© 2011 Wiley利斯公司
Maternal infection during pregnancy is an environmental risk factor for the offspring to develop severe brain disorders, including schizophrenia. However, little is known about the neurodevelopmental mechanisms underlying the association between prenatal exposure to infection and emergence of cognitive and behavioral dysfunctions later in life. By injecting the viral mimetic polyriboinosinic‐polyribocytidylic acid (Poly I:C) into mice, we investigated the influence of maternal immune challenge during pregnancy on the development of the cerebral cortex, a responsive organ for cognition. Stimulation of the maternal immune system did not influence the cell number or density of the cortical neurons of postnatal 10‐day‐old and 8‐week‐old offspring, whereas gene expressions of upper‐layer‐specific transcription factors were significantly reduced, without affecting those of the deeper‐layer ones. Moreover, the prenatal Poly I:C injection impaired synaptic development of the upper‐layer neurons at a later stage, and there was a decrease in the synaptophysin‐ and glutamic acid decarboxylase‐67‐positive puncta surrounding the neuronal cell bodies and an increase in the dendritic spine density in postnatal 8‐week‐old offspring. Considering their importance for cognitive function, the specific abnormalities in the development of upper‐layer neuronal phenotypes may underlie the development of psychiatric brain and behavioral dysfunctions emerging after in utero exposure to an infection. © 2011 Wiley‐Liss, Inc.