In utero exposure to brief hyperthermia interferes with the production and migration of neocortical neurons and induces apoptotic neuronal death in the fetal mouse brain

In utero exposure to brief hyperthermia interferes with the production and migration of neocortical neurons and induces apoptotic neuronal death in the fetal mouse brain
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DOI:
10.1016/s0165-3806(01)00295-4
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发表时间:
2001-12-14
期刊:
DEVELOPMENTAL BRAIN RESEARCH
影响因子:
--
通讯作者:
Shiota, K
Shiota, K
中科院分区:
其他
文献类型:
--
作者:
Hinoue, A;Fushiki, S;Shiota, K

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为了探讨母体高温引起的脑发育不良的发病机制,我们在妊娠第13.5或14.5天将怀孕的ICR小鼠暴露在43℃下12.5分钟,并检查其胎儿端脑中神经元前体细胞的增殖和迁移。治疗后 72 小时检查时,热应激胎儿的脑重量显着下降。组织学检查显示,加热组的新皮质厚度,特别是中间(迁移)区和皮质板的厚度减少。 BrdU/抗BrdU免疫组织化学显示,热疗后基质细胞区的细胞增殖被抑制长达8小时,并且BrdU标记的神经元从基质细胞区向原始皮质的迁移显着减慢。此外,在治疗后8-12小时,热应激胎儿大脑中细胞凋亡增加,这在对照组动物的大脑中很少观察到。因此,神经元分化关键阶段的短暂高温似乎会干扰神经元前体细胞的产生和迁移,并导致大脑发育异常和神经行为障碍。 (C) 2001 年由 Elsevier Science B.V. 出版
To investigate the pathogenetic mechanisms of brain maldevelopment induced by maternal hyperthermia, we exposed pregnant ICR mice to 43degreesC for 12.5 min on day 13.5 or 14.5 of gestation and examined the proliferation and migration of neuronal precursor cells in the telencephalon of their fetuses. The brain weight was significantly decreased in heat-stressed fetuses when examined at 72 h after treatment. Histological examination revealed that the thickness of the neopallium, especially that of the intermediate (migratory) zone and the cortical plate, was decreased in the heated group. BrdU/anti-BrdU immunohistochemistry showed that cell proliferation in the matrix cell zone was suppressed for up to 8 h after hyperthermia and that the migration of BrdU-labeled neurons from the matrix cell zone to the primordial cortex was decelerated significantly. In addition, apoptotic cell death which is rarely observed in the brain of control animals increased in the brain of heat-stressed fetuses at 8-12 h after treatment. Thus, it seems that brief hyperthermia at critical stages of neuronal differentiation can interfere with the production and migration of neuronal precursor cells and result in abnormal brain development and neurobehavioural disturbances. (C) 2001 Published by Elsevier Science B.V.