癌变·畸变·突变2025，Vol.37Issue(5)：345-352,8.DOI:10.3969/j.issn.1004-616x.2025.05.001
慢性低剂量钴暴露对人大脑类器官的神经毒性研究
Neurotoxicity of chronic low-dose cobalt exposure in human cerebral organoids
摘要
Abstract
OBJECTIVE:To investigate neurotoxic effects of chronic cobalt exposure on human cerebral organoids and to provide experimental evidence for assessing potential health risks of heavy metal cobalt.METHODS:Human iPSC-derived cerebral organoids at day 28 of differentiation were randomly divided into the control group,5,10,and 20 μmol/L CoCl2 exposure groups,with continuous exposure for 28 days.Samples of human cerebral organoids were collected on day 56.Immunofluorescence staining was used to systematically characterize the differentiation status(SOX2/TBR2/CTIP2/TUJ1/NeuN/SYN1),expression of hypoxia-inducible factor-1α,cellular hypoxia status(Hypoxyprobe),proliferation and apoptosis levels(Ki-67/TUNEL),and astrocyte damage(GFAP)of human cerebral organoids.RESULTS:Day56 organoids maintained high proliferative activity.Neural progenitor cells self-organized into ventricular zone-like structures,forming physiological lamellar architectures with intermediate progenitors and deep-layer cortical neurons.Chronic cobalt exposure significantly upregulated HIF-1α protein expression(P<0.01)and increased hypoxic cells versus controls.TUNEL-positive apoptotic cells showed dose-dependent elevation(P<0.01),predominantly localized in intermediate progenitor/neuron interface regions.Bright-field monitoring revealed progressive disintegration of ventricular zone structures in medium/high-dose groups.GFAP fluorescence intensity was markedly attenuated in exposure groups,indicating astrocyte impairment.CONCLUSION:Chronic cobalt exposure stabilizes HIF-1α to induce pseudohypoxia,leading to three neurotoxic outcomes:increased neuronal apoptosis,ventricular zone collapse,and astrocyte damage.关键词
钴/人大脑类器官/缺氧诱导因子-1α/神经毒性Key words
cobalt/human cerebral organoids/HIF-1α/neurotoxicity分类
医药卫生引用本文复制引用
郭新华,黄琰,陈琪琪,鲁诗雅,曾品利,王志秋,李灏,卜迁..慢性低剂量钴暴露对人大脑类器官的神经毒性研究[J].癌变·畸变·突变,2025,37(5):345-352,8.基金项目
国家自然科学基金原创探索计划项目(T2350007) （T2350007）
