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Updated: Dec 11, 2025
Three-Dimensional Motor Nerve Organoid Generation
Published on: September 24, 2020
Multi-walled carbon nanotubes decrease neuronal NO synthase in 3D brain organoids.
Ying Jiang1, Housheng Gong1, Shaohua Jiang2
1Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province and Key Laboratory of Hunan Higher Education for Western Hunan Medicinal Plant and Ethnobotany, Huaihua University, Huaihua 418008, China; Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Lab of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
Multi-walled carbon nanotubes (MWCNTs) harm human brain organoids by reducing neuronal nitric oxide synthase (nNOS) activity. This occurs through oxidative stress and altering NF-κB and KLF4 pathways, impacting brain function.
Area of Science:
- Neuroscience
- Toxicology
- Biotechnology
Background:
- Multi-walled carbon nanotubes (MWCNTs) are linked to neuronal nitric oxide synthase (nNOS) dysfunction, but traditional models may not represent human brain complexity.
- Human induced pluripotent stem cell-derived 3D brain organoids offer a novel in vitro model for studying human brain responses.
Purpose of the Study:
- To investigate the toxic effects of MWCNTs on 3D human brain organoids.
- To elucidate the underlying mechanisms of MWCNT-induced neurotoxicity.
Main Methods:
- Exposure of 3D brain organoids to varying concentrations of MWCNTs.
- Measurement of intracellular nitric oxide (NO) and superoxide levels.
- Analysis of nNOS, NF-κB, and KLF4 protein expression.
- Fluorescence micro-optical sectioning tomography (MOST) for protein localization.
Main Results:
- MWCNTs induced cytotoxicity in 3D brain organoids, not in a dose-dependent manner.
- High MWCNT levels reduced intracellular NO and increased superoxide, decreasing nNOS protein.
- MWCNTs modulated nNOS regulators, inducing NF-κB and reducing KLF4, with effects seen in inner and outer organoid layers.
Conclusions:
- MWCNTs impair nNOS activity in human brain organoids via oxidative stress and modulation of the NF-κB-KLF4 pathway.
- 3D brain organoids are a valuable tool for mechanism-based toxicology studies of nanomaterials.
