海马结构
铅(地质)
认知
铅暴露
小胶质细胞
海马体
神经科学
重金属
体内
生物信息学
生理学
生物
医学
化学
内科学
遗传学
环境化学
炎症
古生物学
猫
作者
Yingsi Cao,Wenjing Zhao,Yanqi Zhong,Xiaofan Jiang,Huiya Mei,Yuanjin Chang,Dongqin Wu,Jianrui Dou,Emely Vasquez,Xian Shi,Jiatao Yang,Zhongtang Jia,Xiaochao Tan,Qian Li,Yuying Dong,Ruijin Xie,Ju Gao,Yu Wu,Yueying Liu
标识
DOI:10.1016/j.scitotenv.2024.170317
摘要
Lead (Pb), a pervasive and ancient toxic heavy metal, continues to pose significant neurological health risks, particularly in regions such as Southeast Asia. While previous research has primarily focused on the adverse effects of acute, high-level lead exposure on neurological systems, studies on the impacts of chronic, low-level exposure are less extensive, especially regarding the precise mechanisms linking ferroptosis — a novel type of neuron cell death — with cognitive impairment. This study aims to explore the potential effects of chronic low-level lead exposure on cognitive function and hippocampal neuronal ferroptosis. This research represents the first comprehensive investigation into the impact of chronic low-level lead exposure on hippocampal neuronal ferroptosis, spanning clinical settings, bioinformatic analyses, and experimental validation. Our findings reveal significant alterations in the expression of genes associated with iron metabolism and Nrf2-dependent ferroptosis following lead exposure, as evidenced by comparing gene expression in the peripheral blood of lead-acid battery workers and workers without lead exposure. Furthermore, our in vitro and in vivo experimental results strongly suggest that lead exposure may precipitate cognitive dysfunction and induce hippocampal neuronal ferroptosis. In conclusion, our study indicates that chronic low-level lead exposure may activate microglia, leading to the promotion of ferroptosis in hippocampal neurons.
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