Wang Xueting, Yang Xin, He Weifeng, Zhang Shixuan, Song Xin, Zhang Junrou, Ma Junxiang, Chen Li, Niu Piye, Chen Tian
Department of Occupational Health 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 Health 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.
Environ Pollut. 2024 Jan 15;341:122908. doi: 10.1016/j.envpol.2023.122908. Epub 2023 Nov 10.
Manganese (Mn) is considered as an important environmental risk factor for Parkinson's disease. Excessive exposure to Mn can damage various neural cells and affect the neurogenesis, resulting in neurological dysfunction. However, the specific mechanisms of Mn exposure affecting neurogenesis have not been well understood, including compositional changes and heterogeneity of various neural cells. Zebrafish have been successfully used as a neurotoxicity model due to its homology with mammals in several key regions of the brain, as well as its advantages such as small size. We performed single-cell RNA sequencing of zebrafish brains from normal and Mn-exposed groups. Our results suggested that low levels of Mn exposure activated neurogenesis in the zebrafish brain, including promoting the proliferation of neural progenitor cells and differentiation to newborn neurons and oligodendrocytes, while high levels of Mn exposure inhibited neurogenesis and neural function. Mn could affect neurogenesis through specific molecular pathways. In addition, Mn regulated intercellular communication and affected cellular communication in neural cells through specific signaling pathways. Taken together, our study elucidates the cellular composition of the zebrafish brain and adds to the understanding of the mechanisms involved in Mn-induced neurogenesis damage.
锰（Mn）被认为是帕金森病的一个重要环境风险因素。过度接触锰会损害各种神经细胞并影响神经发生，导致神经功能障碍。然而，锰暴露影响神经发生的具体机制尚未完全明确，包括各种神经细胞的组成变化和异质性。斑马鱼因其在大脑几个关键区域与哺乳动物具有同源性以及体型小等优势，已成功用作神经毒性模型。我们对正常组和锰暴露组的斑马鱼大脑进行了单细胞RNA测序。我们的结果表明，低水平的锰暴露激活了斑马鱼大脑中的神经发生，包括促进神经祖细胞的增殖以及向新生神经元和少突胶质细胞的分化，而高水平的锰暴露则抑制神经发生和神经功能。锰可通过特定分子途径影响神经发生。此外，锰通过特定信号通路调节细胞间通讯并影响神经细胞中的细胞通讯。综上所述，我们的研究阐明了斑马鱼大脑的细胞组成，并增进了对锰诱导神经发生损伤所涉及机制的理解。
