Long-term exposure to cadmium disrupts neurodevelopment in mature cerebral organoids

• Published in: The Science of the total environment Vol. 912; p. 168923
• Main Authors: Huang, Yan, Guo, Xinhua, Lu, Shiya, Chen, Qiqi, Wang, Zhiqiu, Lai, Li, Liu, Qian, Zhu, Xizhi, Luo, Li, Li, Jiayuan, Huang, Yina, Gao, Hong, Zhang, Zunzhen, Bu, Qian, Cen, Xiaobo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.02.2024
• Subjects: Animals; Cadmium; Cadmium - metabolism; Cortical layer; Environmental Pollutants - metabolism; Environmental Pollutants - toxicity; Female; Humans; Neural differentiation; Neural Stem Cells; Neurons; Organoids - metabolism; Pregnancy; Synaptic signaling; Zinc - metabolism; Zinc and copper ion homeostasis; Cortical layer; Cadmium; Synaptic signaling; Neural differentiation; Zinc and copper ion homeostasis
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2023.168923

Cadmium (Cd) is a pervasive environmental pollutant. Increasing evidence suggests that Cd exposure during pregnancy can induce adverse neurodevelopmental outcomes. However, due to the limitations of neural cell and animal models, it is challenging to study the developmental neurotoxicity and underlying toxicity mechanism of long-term exposure to environmental pollutants during human brain development. In this study, chronic Cd exposure was performed in human mature cerebral organoids for 49 or 77 days. Our study found that prolonged exposure to Cd resulted in the inhibition of cerebral organoid growth and the disruption of neural differentiation and cortical layer organization. These potential consequences of chronic Cd exposure may include impaired GFAP expression, a reduction in SOX2+ neuronal progenitor cells, an increase in TUJ1+ immature neurons, as well as an initial increase and a subsequent decrease in both TBR2+ intermediate progenitors and CTIP2+ deep layer cortical neurons. Transcriptomic analyses revealed that long-term exposure to Cd disrupted zinc and copper ion homeostasis through excessive synthesis of metallothionein and disturbed synaptogenesis, as evidenced by inhibited postsynaptic protein. Our study employed mature cerebral organoids to evaluate the developmental neurotoxicity induced by long-term Cd exposure. [Display omitted] •Long-term exposure to cadmium impaired neurodevelopment in cerebral organoids.•Cadmium exposure hampered the growth of neuronal progenitors and astrocytes.•Chronic cadmium exposure disrupted the structural integrity of cortical layers.•Synaptic signaling was negatively influenced by prolonged cadmium exposure.