Garg Asmita, Bandyopadhyay Sanghamitra
Systems Toxicology Group, Food, Drug & Chemical, Environment and Systems Toxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Systems Toxicology Group, Food, Drug & Chemical, Environment and Systems Toxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Chemosphere. 2025 Mar;372:144046. doi: 10.1016/j.chemosphere.2024.144046. Epub 2025 Jan 22.
The review aims to examine the neurotoxic effects of arsenic, particularly exploring the roles of glial cells-astrocytes, microglia, and oligodendrocytes, amid its widespread environmental contamination and impact on cognitive impairments. It highlights the role of altered neurotrophin and growth factor signaling in disrupting neuronal health and cognitive performance. It elucidates the intricate interactions between oxidative stress, DNA damage, neurotransmitter disruption, and cellular signaling alterations, underscoring the vital importance of the glial cells. These cells are crucial for preserving neural health and responding to environmental toxins, and arsenic disrupts their functions, resulting in decreased antioxidative responses, induction of inflammatory pathways, and subsequent neuronal dysfunction. The brain's cytotoxic impact arises from a complex network of cellular responses, with pathways such as MAPK, transcription factor and autophagy signaling to play critical roles in mediating these dysregulated inflammation and oxidative stress mechanisms. The detailed exploration into specific impacts of arsenic on glial cell morphology, activation, and mitochondrial functions illuminates the cascade of neuroinflammatory and neurodegenerative changes that may be triggered upon arsenic exposure. The review recommends a multidisciplinary research approach by emphasizing the significance of the brain's microenvironment, methylation processes, and the enzyme AS3MT in arsenic neurotoxicity. It calls for converging environmental science, neurobiology, and toxicology to develop targeted interventions for preventing and mitigating arsenic's neurotoxic effects. This in-depth exploration into glial cell dynamics aims to advance public health and neurotoxicology research, striving to devise strategies that reduce the cognitive and neurodegenerative damage caused by arsenic, thereby enhancing global health outcomes.
本综述旨在研究砷的神经毒性作用，特别是在其广泛的环境污染及其对认知障碍的影响背景下，探讨神经胶质细胞（星形胶质细胞、小胶质细胞和少突胶质细胞）所起的作用。它强调了神经营养因子和生长因子信号改变在破坏神经元健康和认知表现方面的作用。它阐明了氧化应激、DNA损伤、神经递质紊乱和细胞信号改变之间的复杂相互作用，突出了神经胶质细胞的至关重要性。这些细胞对于维持神经健康和应对环境毒素至关重要，而砷会破坏它们的功能，导致抗氧化反应降低、炎症途径的诱导以及随后的神经元功能障碍。大脑的细胞毒性影响源于复杂的细胞反应网络，其中丝裂原活化蛋白激酶（MAPK）、转录因子和自噬信号等途径在介导这些失调的炎症和氧化应激机制中发挥关键作用。对砷对神经胶质细胞形态、活化和线粒体功能的具体影响的详细探索，揭示了砷暴露后可能引发的神经炎症和神经退行性变化的级联反应。该综述强调大脑微环境、甲基化过程和酶AS3MT在砷神经毒性中的重要性，建议采用多学科研究方法。它呼吁整合环境科学、神经生物学和毒理学，以制定有针对性的干预措施，预防和减轻砷的神经毒性作用。对神经胶质细胞动态变化的深入探索旨在推动公共卫生和神经毒理学研究，努力设计出减少砷引起的认知和神经退行性损伤的策略，从而改善全球健康状况。
