Maternal immune activation by poly (I:C) exposure causes cerebral cortical dysgenesis through dysregulated cell cycle kinetics of neural stem/progenitor cells.
Maternal immune activation by poly (I:C) exposure causes cerebral cortical dysgenesis through dysregulated cell cycle kinetics of neural stem/progenitor cells.
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暴露于聚 (I:C) 的母体免疫激活通过神经干/祖细胞的细胞周期动力学失调导致大脑皮质发育不全。
DOI：
10.1159/000529317
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Takahashi T.
中科院分区：
文献类型：
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作者：
Sasaki M;Mitsuhashi T;Goto F;Shibata S;Kubo K;Oku S;Owashi A;Takahashi T.
据报道，母体免疫激活导致干细胞中细胞周期的失调，以及啮齿动物中高级皮质功能的损害。此外，在人类中，在怀孕的第一至第二个三个月期间的母体免疫激活与后代中自闭症谱系障碍的发病率增加密切相关。在这里，我们表明，在子宫内暴露于多聚肌苷酸，多聚胞苷酸（聚（I：C））在小鼠神经元发生的早期阶段增加的分化的可能性（Q分数）的神经干/祖细胞（NSPCs）的细胞周期的长度没有变化。假设Q分数的这种异常增加降低了NSPCs的峰值群体大小，由于神经元的产生减少，导致后代的新皮层变薄。此外，聚（I：C）暴露小鼠的新皮质没有表现出径向厚度的层特异性减少，可能是因为在皮质发育的所有阶段聚（I：C）暴露引起的细胞凋亡增加。这些结果表明，母体免疫激活聚（I：C）曝光可能会影响新皮质组织发生通过改变细胞周期动力学的NSPCs。此外，怀孕期间暴露于多聚（I：C）的时间和数量可能对大脑皮质组织发生产生深远的影响。
Maternal immune activation reportedly causes dysregulation of the cell cycle in stem cells, and impairment of higher cortical function in rodents. Furthermore, in humans’ maternal immune activation during the first to second trimester of pregnancy is strongly correlated with increased incidence of autism spectrum disorder in the offspring. Here, we show that in utero exposure to polyinosinic-polycytidylic acid (poly (I: C)) in mice during the early phase of neuronogenesis increases the probability of differentiation (Q fraction) of neural stem/progenitor cells (NSPCs) without change in the length of cell cycle. This abnormal increase in the Q fraction is assumed to reduce the peak population size of NSPCs, resulting in a thinning of the neocortex in offspring because of the reduced production of neurons. Furthermore, the neocortex of poly (I: C)-exposed mice does not exhibit a layerspecific reduction in radial thickness, possibly because of increased apoptosis caused by poly (I: C) exposure during all stages of cortical development. These results suggest that maternal immune activation by poly (I: C) exposure may affect neocortical histogenesis by altering the cell cycle kinetics of NSPCs. In addition, the timing and amount of poly (I: C) exposure during pregnancy may have profound effects on cerebral cortical histogenesis.