Abstract：
Neural tube malformation is a common kind of human birth defect. High temperature is one of the most common physical teratogenic factors. Several studies have suggested that heat stress may cause neurotoxicity during brain development, but more studies are warranted to reveal the mechanism and draw consistent conclusions. The current study used a cell model of primary mouse embryonic neural stem/progenitor cells (NSPCs) subjected to heat stress of 43 °C for 20 min. Our study investigated the changes in the NSPCs transcriptome under heat stress using high-throughput mRNA-seq. The NSPCs showed remarkably altered genes associated with cell growth, proliferation, cell cycle, and survival when exposed to heat stress. Heat stress reduced cell viability, proliferation, and neurosphere formation and caused cell cycle arrest and apoptosis in cultured NSPCs. PCR arrays confirmed that the TNF receptor family plays an important role in the apoptosis of NSPCs during heat stress. The results of real-time PCR confirmed that heat stress affects the expression of critical genes. We provide transcriptomic insight into heat stress-induced developmental neurotoxic effects and the underlying mechanisms.
摘要：
神经管畸形是人类常见的一种出生缺陷。高温是最常见的物理致畸因素之一。几项研究表明，热应激可能会在大脑发育过程中引起神经毒性，但是有必要进行更多的研究来揭示这种机制并得出一致的结论。当前的研究使用了原代小鼠胚胎神经干/祖细胞（NSPC）的细胞模型，该模型经受了43°C的热应激20分钟。我们的研究使用高通量mRNA-seq调查了热应激下NSPCs转录组的变化。NSPCs显示与细胞生长相关的基因显著改变，扩散,细胞周期,和生存时暴露在热应激。热应激降低细胞活力，扩散,和神经球形成，并导致培养的NSPCs细胞周期停滞和凋亡。PCR阵列证实，TNF受体家族在热应激期间NSPCs的凋亡中起重要作用。实时PCR结果证实热应激影响关键基因的表达。我们提供了对热应激诱导的发育神经毒性作用和潜在机制的转录组学见解。
