Notch信号通路介导的神经干细胞自噬在铅神经毒性中的重要作用

重金属铅污染是我国普遍存在的环境问题，影响着人类的健康。铅对神经系统损伤尤为严重，但对于铅暴露引起的神经毒性的具体机制尚未阐明。神经干细胞是一类具有增殖分化功能的神经细胞，它与神经系统的功能关系密切。自噬是细胞内维持内环境稳定的一种生理机制，然而过度的自噬则能够导致细胞死亡。我们之前的研究指出，铅暴露能够诱导自噬水平升高诱导海马神经元死亡。但铅暴露后神经干细胞自噬水平的改变是否发生并无报道，是否铅暴露后神经干细胞的损伤与自噬相关值得我们进一步研究。mTOR被认为是调控自噬的重要分子， Notch信号通路近年来被发现与mTOR共同调控自噬。因此，研究铅暴露后mTOR-Notch信号通路的改变可能为揭示铅损伤神经干细胞的机制提供有力线索。本项目结合国内外相关机制的研究进展，拟通过对铅暴露后神经干细胞自噬的发生以及Notch信号通路对其的调控作用，揭示神经干细胞在铅神经毒性中的关键作用及机制。

Heavy metal lead pollution is a ubiquitous environmental problem in our country, affecting the health of human beings.Lead damage to the nervous system is particularly serious, but for the specific mechanism of neurotoxicity caused by lead exposure has not yet been elucidated.Neural stem cells is a kind of nerve cell proliferation differentiation function, it is closely associated with the function of the nervous system.Autophagy is a cellular maintain stable internal environment of a kind of physiological mechanism, however, excessive autophagy can lead to cell death.Our previous studies have shown that, lead exposure could induce autophagy levels induced hippocampal neuron death.But changes in the level of lead exposure after neural stem cell autophagy, whether there is no reported whether lead exposure of neural stem cells after injury associated with autophagy is worth our further research.MTOR is considered important molecular regulation of autophagy, Notch signal pathway was found in recent years and mTOR common regulation of autophagy.So the lead exposure mTOR - after the change of the Notch signal pathway may lead to reveal the damage mechanism of neural stem cells provide strong clues.The research progress of the project combining with domestic and foreign relevant mechanism, proposed based on the neural stem cells following exposure to lead the occurrence of autophagy and the Notch signaling pathway of its regulation function, reveal the key role of neural stem cells in lead neurotoxicity and mechanism.