铅是一种神经毒性重金属元素，其对中枢神经系统造成的损伤是不可逆的。铅中毒可以导致儿童认知能力降低和行为学改变。目前针对铅的神经毒性机制研究多集中于认知能力方面，尚无针对行为学改变机制的研究。本课题前期研究发现铅可导致幼鼠脑组织中参与调控机体行为的PV中间神经元数量减少，结合基因芯片结果和文献报道，Dlx5/6基因可能在调控该神经元增殖分化中起重要作用。因此推测：铅可能通过下调Dlx5/6使PV中间神经元减少，最终导致行为发生改变。本次研究拟通过从细胞和动物水平敲除/转染Dlx5/6基因等实验观察PV中间神经元数量及功能变化，以确定该基因的作用；并通过检测儿童脑组织中与PV中间神经元相关的γ-GABA和5-HT两个指标的释放情况，判断人体内中间神经元是否也存在同样的改变，进而将揭示儿童铅中毒诱发行为学改变的重要分子机制，为治疗这一毒性作用提供坚实可靠的理论基础。

Lead as a neurotoxic heavy metal,can make irreversible injuries to the central nervous system. Lead poisoning can lead to reducing children's cognitive and behavioral changes. For the mechanism of lead neurotoxicity ,many studies have been focued on cognitive decline,but no one fouced on behavioral change. Our previous study had found that the lead can reduce the number of PV internuncial neuron which involved in the regulation of body behaviour by experimentation on animals.Although the regulatory mechanism is not yet clear, the combine of gene chip and literature, Dlx5 / 6 genes maybe is a important factor that can regulates the proliferation and differentiation of PV internuncial neuron. Therefore, we speculate that lead thoughout down-regulating Dlx5 /6 to make decreasing of PV intermediate ,then eventually lead to larval behavior and personality changes. Therefore,we want to knockout or transfection Dlx5 / 6 from the level of cells and organs to observate the PV quantity and functional changes in intermediate neurons; we also take a follow-up on children lead levels and test the level of neurotransmittes,such as γ-GABA, 5-HT and so on ,in order to determine the initial intermediate neurons of the human body . This study will reveal important molecular mechanism of childhood behavioral changes induced by lead poisoning and provide solid theoretical foundation for the treatment of the toxic effects.