铝作为一种常见的神经毒物，主要表现为学习记忆功能降低，并表现为突触可塑性改变。miR-29能够引起神经元突起数量增加，轴突生长，与突触可塑性有关。前期研究发现铝暴露可致大鼠海马miR-29含量改变，可能会影响其靶基因PTEN的表达，影响对PI3K/Akt信号通路的负性调控，影响GSK-3β的活性，进而影响AMPA受体的表达，最后降低突触传递效能。本研究拟通过体内实验、侧脑室立体定位实验及体外实验建立铝中毒及干预模型，测定神经元LTP变化、miR-29变化、PTEN及GSK-3β信号通路相关分子的变化；旨在探索miR-29调控的PTEN及GSK-3β信号通路在铝致突触可塑性损伤中的作用，从miRNA水平阐明铝的神经毒性，为铝致认知功能损害机理提供新资料，并尝试将上述分子作为铝致神经毒性生物标志物。

Aluminum is a widely exposed neurotoxicant. Excessive exposure to aluminum induces cognitive impairment. Synaptic plasticity impairment is main toxic mechanism caused by aluminum.The role of miRNAs in diseases of the nervous system is a hotspot in recent years.miR-29 can regulate the protuberant number of neurons and the growth of axon, further miR-29 is associated with synaptic plasticity. Previous study have found that aluminum can cause the change of miR-29 , might affect its target gene PTEN, might affect PI3K/Akt signaling pathways regulated by PTEN negatively, lead to the change of the activity of GSK-3 beta, then influence the expression of AMPA receptors, finally reduce synaptic transmission efficiency. This research will establish aluminum- exposed model and intervention model through in vivo study, Lateral ventricle stereotaxic injection study and in vitro study. Further detect the change of LTP in neuro, observe the chang of miR-29, PTEN and GSK-3beta signaling pathway related moleculars. This research aims to investigate aluminum- induced neurotoxicity from the viewpoint of miRNA, to explore the mechanism of miR-29 on GSK-3β signaling pathway regulated by PTEN in the synaptic plasticity injury induced by aluminum exposure. Furthermore, This research not only provides new informations for investigating the mechanism of aluminum- induced cognitive impaiment, but also try to take these moleculars as biomarkers for aluminum- induced neurotoxicity.