Practical Teaching Centre, School of Forensic Medicine, China Medical University, Shenyang, People's Republic of China.
Department of Orthopaedics, The First Hospital, China Medical University, Shenyang, People's Republic of China.
Brain Res. 2021 Feb 1;1752:147234. doi: 10.1016/j.brainres.2020.147234. Epub 2021 Jan 5.
With the industrial development and progressive increase in environmental pollution, the mankind overexposure to heavy metals emerges as a pressing public health issue. Excessive intake of heavy metals, such as arsenic (As), manganese (Mn), mercury (Hg), aluminium (Al), lead (Pb), nickel (Ni), bismuth (Bi), cadmium (Cd), copper (Cu), zinc (Zn), and iron (Fe), is neurotoxic and it promotes neurodegeneration. Astrocytes are primary homeostatic cells in the central nervous system. They protect neurons against all types of insults, in particular by accumulating heavy metals. However, this makes astrocytes the main target for heavy metals neurotoxicity. Intake of heavy metals affects astroglial homeostatic and neuroprotective cascades including glutamate/GABA-glutamine shuttle, antioxidative machinery and energy metabolism. Deficits in these astroglial pathways facilitate or even instigate neurodegeneration. In this review, we provide a concise outlook on heavy metal-induced astrogliopathies and their association with major neurodegenerative disorders. In particular, we focus on astroglial mechanisms of iron-induced neurotoxicity. Iron deposits in the brain are detected in main neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Accumulation of iron in the brain is associated with motor and cognitive impairments and iron-induced histopathological manifestations may be considered as the potential diagnostic biomarker of neurodegenerative diseases. Effective management of heavy metal neurotoxicity can be regarded as a potential strategy to prevent or retard neurodegenerative pathologies.
随着工业的发展和环境污染的逐步加剧，人类过度暴露于重金属成为一个紧迫的公共卫生问题。过量摄入重金属，如砷（As）、锰（Mn）、汞（Hg）、铝（Al）、铅（Pb）、镍（Ni）、铋（Bi）、镉（Cd）、铜（Cu）、锌（Zn）和铁（Fe），具有神经毒性，并促进神经退行性变。星形胶质细胞是中枢神经系统中的主要内稳态细胞。它们保护神经元免受各种损伤，特别是通过积累重金属。然而，这使得星形胶质细胞成为重金属神经毒性的主要靶点。重金属的摄入会影响星形胶质细胞的内稳态和神经保护级联反应，包括谷氨酸/GABA-谷氨酰胺穿梭、抗氧化机制和能量代谢。这些星形胶质细胞途径的缺陷会促进或甚至引发神经退行性变。在这篇综述中，我们提供了一个关于重金属诱导的星形胶质细胞病及其与主要神经退行性疾病关联的简要概述。特别是，我们关注铁诱导的神经毒性的星形胶质细胞机制。在阿尔茨海默病、帕金森病和肌萎缩侧索硬化症等主要神经退行性疾病中，都检测到了大脑中的铁沉积。大脑中铁的积累与运动和认知障碍有关，铁诱导的组织病理学表现可能被认为是神经退行性疾病的潜在诊断生物标志物。有效管理重金属神经毒性可以被视为预防或延缓神经退行性病变的潜在策略。
