PUBLICATION
Multi-omics analysis of a drug-induced model of bipolar disorder in zebrafish
- Authors
- Li, Y., Zhang, L., Mao, M., He, L., Wang, T., Pan, Y., Zhao, X., Li, Z., Mu, X., Qian, Y., Qiu, J.
- ID
- ZDB-PUB-230520-32
- Date
- 2023
- Source
- iScience 26: 106744106744 (Journal)
- Registered Authors
- Keywords
- Behavioral neuroscience, Lipidomics, Metabolomics, Molecular neuroscience, Techniques in neuroscience, Transcriptomics
- MeSH Terms
- none
- PubMed
- 37207274 Full text @ iScience
Citation
Li, Y., Zhang, L., Mao, M., He, L., Wang, T., Pan, Y., Zhao, X., Li, Z., Mu, X., Qian, Y., Qiu, J. (2023) Multi-omics analysis of a drug-induced model of bipolar disorder in zebrafish. iScience. 26:106744106744.
Abstract
Emerging studies demonstrate that inflammation plays a crucial role in the pathogenesis of bipolar disorder (BD), but the underlying mechanism remains largely unclear. Given the complexity of BD pathogenesis, we performed high-throughput multi-omic profiling (metabolomics, lipidomics, and transcriptomics) of the BD zebrafish brain to comprehensively unravel the molecular mechanism. Our research proved that in BD zebrafish, JNK-mediated neuroinflammation altered metabolic pathways involved in neurotransmission. On one hand, disturbed metabolism of tryptophan and tyrosine limited the participation of the monoamine neurotransmitters serotonin and dopamine in synaptic vesicle recycling. On the other hand, dysregulated metabolism of the membrane lipids sphingomyelin and glycerophospholipids altered the synaptic membrane structure and neurotransmitter receptors (chrnα7, htr1b, drd5b, and gabra1) activity. Our findings revealed that disturbance of serotonergic and dopaminergic synaptic transmission mediated by the JNK inflammatory cascade was the key pathogenic mechanism in a zebrafish model of BD, provides critical biological insights into the pathogenesis of BD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping