Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Ecotoxicol Environ Saf. 2023 Mar 15;253:114616. doi: 10.1016/j.ecoenv.2023.114616. Epub 2023 Feb 14.
Manganese (Mn) accumulates in the central nervous system and can cause neurotoxicity, but the mechanisms of Mn-induced neurotoxicity remain unclear. We performed single-cell RNA sequencing (scRNA-seq) of zebrafish brain after Mn exposure and identified 10 cell types by marker genes: cholinergic neurons, dopaminergic (DA) neurons, glutaminergic neurons, GABAergic neurons, neuronal precursors, other neurons, microglia, oligodendrocyte, radial glia, and undefined cells. Each cell type has its distinct transcriptome profile. Pseudotime analysis revealed that DA neurons had a critical role in Mn-induced neurological damage. Combined with metabolomic data, chronic Mn exposure significantly impaired amino acid and lipid metabolic processes in the brain. Furthermore, we found that Mn exposure disrupted the ferroptosis signaling pathway in the DA neurons in zebrafish. Overall, our study employed joint analysis of multi-omics and revealed ferroptosis signaling pathway is a novel potential mechanism of Mn neurotoxicity.
锰（Mn）在中枢神经系统中积累，可引起神经毒性，但锰诱导的神经毒性的机制仍不清楚。我们对暴露于锰后的斑马鱼大脑进行了单细胞 RNA 测序（scRNA-seq），并通过标记基因鉴定出 10 种细胞类型：胆碱能神经元、多巴胺（DA）神经元、谷氨酸能神经元、γ-氨基丁酸能神经元、神经元前体、其他神经元、小胶质细胞、少突胶质细胞、放射状胶质细胞和未定义细胞。每种细胞类型都有其独特的转录组特征。假性时间分析表明，DA 神经元在锰诱导的神经损伤中起关键作用。结合代谢组学数据，慢性锰暴露显著损害了大脑中的氨基酸和脂质代谢过程。此外，我们发现锰暴露破坏了斑马鱼中 DA 神经元的铁死亡信号通路。总的来说，我们的研究采用了多组学联合分析，揭示了铁死亡信号通路是锰神经毒性的一个新的潜在机制。
