PUBLICATION
Lurasidone induces developmental toxicity and behavioral impairments in zebrafish embryos
- Authors
- Li, W., Wang, F., Feng, Z., Cheng, Q., Huang, Y., Zhu, L., Xiao, H., Gong, H.
- ID
- ZDB-PUB-250716-8
- Date
- 2025
- Source
- Frontiers in psychiatry 16: 15815241581524 (Journal)
- Registered Authors
- Keywords
- behavioral toxicology, lurasidone, neurotoxicity, neurotransmitter systems, zebrafish embryo model
- Datasets
- GEO:GSE299985
- MeSH Terms
- none
- PubMed
- 40666443 Full text @ Front Psychiatry
Citation
Li, W., Wang, F., Feng, Z., Cheng, Q., Huang, Y., Zhu, L., Xiao, H., Gong, H. (2025) Lurasidone induces developmental toxicity and behavioral impairments in zebrafish embryos. Frontiers in psychiatry. 16:15815241581524.
Abstract
Introduction Lurasidone, a second-generation antipsychotic widely used for schizophrenia and bipolar disorder due to its favorable metabolic profile, has poorly understood potential developmental neurotoxicity. This study investigated its effects on zebrafish embryos to address this gap.
Methods Zebrafish embryos were exposed to lurasidone at concentrations of 0, 0.4, 4, and 8 mg/L from 5 to 120 hours post-fertilization (hpf). We integrated morphological assessments, behavioral analyses, transcriptomic profiling, and neurotransmitter quantification to evaluate developmental neurotoxicity.
Results Lurasidone induced dose-dependent developmental toxicity, including reduced survival and hatching rates, decreased body length, and increased pericardial and yolk sac edema. Behavioral assessments revealed significant locomotor impairment and diminished touch response, especially at higher concentrations. Transcriptomic analysis identified 1,907 differentially expressed genes, with upregulation in circadian regulation pathways and downregulation in cell cycle and oxidative phosphorylation pathways. Neurotransmitter profiling showed significant reductions in glutamate, dopamine, and GABA levels.
Discussion These findings demonstrate lurasidone's potential to disrupt neurodevelopment, suggesting perturbations in excitatory/inhibitory neurotransmitter balance and critical cellular pathways. The results highlight neurodevelopmental risks during sensitive periods, underscoring the need for further safety assessment in vulnerable populations (e.g., pregnant women, young patients).
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Human Disease / Model
Sequence Targeting Reagents
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