铝具有明确的神经毒性，可导致明显的认知功能损害，其主要的机制是引起突触可塑性下降和神经元细胞凋亡。研究表明PI3K/AKT/mTOR信号通路激活不仅对神经损伤具有明确的保护作用,而且PI3K/AKT/mTOR通路参与突触可塑性和神经元凋亡的调控。课题组前期研究发现，铝可导致大鼠海马组织37个LncRNA异常表达，其中LNC001209在铝处理组异常下调。而且LNC001209调控的靶基因高度富集在PI3K/AKT/mTOR通路中。我们推测LNC001209通过调控PI3K/AKT/mTOR通路参与铝致认知功能损害的机制。本课题拟采用体外和体内染铝模型，过表达和敲除神经系统中LNC001209，观察其对PI3K/AKT/mTOR通路及神经元突触可塑性和凋亡的影响，探讨LNC001209在铝神经毒性中的作用机制。并在人群中验证这一通路中的关键信号分子，拟找到铝致认知功能损害的早期生物监测指标。

Aluminum is one of definite neurotoxicant, which can lead to obvious cognitive impairment, Al mainly declines synaptic plasticity and induces the apoptosis of neuronal cells. Several Studies have shown that PI3K/AKT/mTOR pathway activation not only has a clear protective effect on nerve damage, but participates in the regulation of synaptic plasticity and neuronal apoptosis. Aluminum can cause abnormal expression of 37 lncRNAs in the hippocampus of rats, of which LNC001209 was significantly reduced in the aluminum treatment group. Moreover, the target genes regulated by LNC001209 are highly enriched in the PI3K/AKT/mToR pathway. We hypothesized that LNC001209 could participate in the mechanism of aluminum induced cognitive impairment by regulating PI3K/AKT/mToR signal pathway. In this study, using SD rat and hippocampus primary cultured neurons exposed by aluminum, we induce overexpression and knock out LNC001209, and observe its effects on PI3K/AKT/mToR pathway and neuronal synaptic plasticity and apoptosis, in order to explore the mechanism of LNC001209 in aluminum induced neurotoxicity, then verify the key signaling molecules in this pathway in the Al-exposed occupational population to find the early monitoring biomarker for aluminum induced cognitive impairment.