High-dose cerium dioxide nanorods induce behavioral and electroencephalographic abnormalities through 5-HT1B receptor signaling disruption with an evaluation of anpirtoline's therapeutic potential.
5 affiliations
- 1Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, China.
- 2Brain Research Innovation and Translation Laboratory, Xuanwu Hospital of Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, China.
- 3Clinical Research Center for Epilepsy, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, China.
- 4National Medical Center for Neurological Diseases, No. 45 Changchun Street, Xicheng District, Beijing, 100053, China.
- 5Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, China.
Abstract
Cerium dioxide nanorods (CeO₂ NRs) have drawn extensive research attention in the past few years for their exceptional generation of reactive oxygen species (ROS) and intrinsic catalytic properties. The two ends of the biological effect show a dose-dependent difference: protection of cells at low doses and damage to cells at high doses. Although the above processes are well documented in other biological contexts, the neurotoxicity induced by acute exposure to CeO₂ NRs, as well as its mechanism and possible prevention strategies, have yet to be elucidated. In the present study, we have found that CeO₂ NRs at a concentration of 500 μg/mL or higher induced neuronal apoptosis and reduced cell viability in vitro. After intranasal instillation in mice, CeO₂ NRs accumulated in the lysosomes and nuclei of neurons in the hippocampus and striatum. There was an increase in these abnormal exploratory behaviors, heightened seizure susceptibility, and altered electroencephalographic (EEG) oscillations. Integrated transcriptomic and proteomic profiling further indicated disruption of serotonin (5-HT) metabolism, caused by a downregulation of the 5-HT1B receptor, and thus provided a possible molecular mechanism for the behaviors and EEG abnormalities observed. Considerable changes also occurred in the various serotonergic mediators, neuronal excitability indicators, and inflammatory markers. Pharmacological activation of the 5-HT1B receptor with anpirtoline partially reversed the behaviors and EEG changes induced by CeO₂ NRs.
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BibTeX
@article{liu2026highdose,
title = {{High-dose cerium dioxide nanorods induce behavioral and electroencephalographic abnormalities through 5-HT1B receptor signaling disruption with an evaluation of anpirtoline's therapeutic potential.}},
author = {Mingshan Liu and Yuedong Li and Chunhao Shen and Hongyi Huang and Quanlei Liu and Bin Fu and Bihan Wu and Xiaomin Wu and Yumin Luo and Yongzhi Shan and Xuegang Niu and Guoguang Zhao},
journal = {Materials today. Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103749},
url = {https://europepmc.org/article/MED/42927304},
note = {CC BY},
}
RIS
TY - JOUR
TI - High-dose cerium dioxide nanorods induce behavioral and electroencephalographic abnormalities through 5-HT1B receptor signaling disruption with an evaluation of anpirtoline's therapeutic potential.
AU - Mingshan Liu
AU - Yuedong Li
AU - Chunhao Shen
AU - Hongyi Huang
AU - Quanlei Liu
AU - Bin Fu
AU - Bihan Wu
AU - Xiaomin Wu
AU - Yumin Luo
AU - Yongzhi Shan
AU - Xuegang Niu
AU - Guoguang Zhao
PY - 2026
DA - 2026/10/14
JO - Materials today. Bio
DO - 10.1016/j.mtbio.2026.103749
UR - https://europepmc.org/article/MED/42927304
AB - Cerium dioxide nanorods (CeO₂ NRs) have drawn extensive research attention in the past few years for their exceptional generation of reactive oxygen species (ROS) and intrinsic catalytic properties. The two ends of the biological effect show a dose-dependent difference: protection of cells at low doses and damage to cells at high doses. Although the above processes are well documented in other biological contexts, the neurotoxicity induced by acute exposure to CeO₂ NRs, as well as its mechanism and possible prevention strategies, have yet to be elucidated. In the present study, we have found that CeO₂ NRs at a concentration of 500 μg/mL or higher induced neuronal apoptosis and reduced cell viability in vitro. After intranasal instillation in mice, CeO₂ NRs accumulated in the lysosomes and nuclei of neurons in the hippocampus and striatum. There was an increase in these abnormal exploratory behaviors, heightened seizure susceptibility, and altered electroencephalographic (EEG) oscillations. Integrated transcriptomic and proteomic profiling further indicated disruption of serotonin (5-HT) metabolism, caused by a downregulation of the 5-HT1B receptor, and thus provided a possible molecular mechanism for the behaviors and EEG abnormalities observed. Considerable changes also occurred in the various serotonergic mediators, neuronal excitability indicators, and inflammatory markers. Pharmacological activation of the 5-HT1B receptor with anpirtoline partially reversed the behaviors and EEG changes induced by CeO₂ NRs.
SN - 2590-0064
ER -