Multi-omics analysis of a drug-induced model of bipolar disorder in zebrafish
Yameng Li,
Lin Zhang,
Mingcai Mao,
Linjuan He,
Tiancai Wang,
Yecan Pan,
Xiaoyu Zhao,
Zishu Li,
Xiyan Mu,
Yongzhong Qian,
Jing Qiu
Affiliations
Yameng Li
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Lin Zhang
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Mingcai Mao
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Linjuan He
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Tiancai Wang
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Yecan Pan
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Xiaoyu Zhao
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Zishu Li
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Xiyan Mu
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Yongzhong Qian
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; Corresponding author
Jing Qiu
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; Corresponding author
Summary: 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.
