PUBLICATION
Disrupted Cholesterol Homeostasis as a Mechanism of Pharmaceutical-Induced Neurodevelopmental Toxicity: A Transgenic Zebrafish Screening Model for abcg1
- Authors
- Zhou, X., Luo, M., Dai, G., Han, X., Yang, F., Qi, C., Jin, X., Lu, M., Wei, L., Zhu, S., Wang, H., Xu, D.
- ID
- ZDB-PUB-250807-1
- Date
- 2025
- Source
- Environmental science & technology : (Journal)
- Registered Authors
- Keywords
- abcg1 transporter, cholesterol homeostasis, environmental pharmaceuticals, neurodevelopmental toxicity, transgenic zebrafish line
- MeSH Terms
-
- ATP Binding Cassette Transporter, Subfamily G, Member 1*/metabolism
- Animals
- Animals, Genetically Modified
- Cholesterol*/metabolism
- Homeostasis/drug effects
- Zebrafish
- PubMed
- 40767573 Full text @ Env. Sci. Tech.
Citation
Zhou, X., Luo, M., Dai, G., Han, X., Yang, F., Qi, C., Jin, X., Lu, M., Wei, L., Zhu, S., Wang, H., Xu, D. (2025) Disrupted Cholesterol Homeostasis as a Mechanism of Pharmaceutical-Induced Neurodevelopmental Toxicity: A Transgenic Zebrafish Screening Model for abcg1. Environmental science & technology. :.
Abstract
With the acceleration of industrialization, increased pharmaceutical consumption, and improper disposal of medications, the accumulation of pharmaceutical residues in the environment has become a global concern, posing significant threats to the neurodevelopment of embryos. Using zebrafish as a model organism, this study evaluated the neurodevelopmental toxicity of prednisone, dexamethasone, acetaminophen, amoxicillin, and azithromycin. The results demonstrated that these pharmaceuticals significantly inhibited embryo hatching, increased mortality, and induced abnormal neurobehavior during the critical developmental window of 36-72 h postfertilization. These effects were accompanied by reduced neuronal cholesterol levels, downregulated neurodevelopmental gene expression, and disrupted cholesterol metabolism. Mechanistic studies revealed that the downregulation of the cholesterol efflux transporter abcg1 is a key factor in pharmaceuticals-induced neurotoxicity. Suppression of abcg1 caused cholesterol accumulation in astrocytes and a deficiency in neurons, resulting in impaired neuronal function and structure. Conversely, overexpression of abcg1 alleviated these toxic effects. Furthermore, a transgenic zebrafish line, Tg(abcg1: EGFP), was developed to enable real-time visualization of abcg1 expression and demonstrated high sensitivity and specificity in detecting neurotoxicants. This study provides a novel tool and perspective for the neurotoxicity assessment of environmental pharmaceuticals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping