Multi-omics analysis of a drug-induced model of bipolar disorder in zebrafish

文献类型： 外文期刊

第一作者： Li, Yameng

作者： Li, Yameng;Zhang, Lin;Mao, Mingcai;He, Linjuan;Wang, Tiancai;Pan, Yecan;Zhao, Xiaoyu;Li, Zishu;Mu, Xiyan;Qian, Yongzhong;Qiu, Jing

作者机构：

期刊名称：ISCIENCE （ 影响因子：5.8； 五年影响因子：5.8 ）

ISSN：

年卷期： 2023 年 26 卷 5 期

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收录情况： SCI

摘要： Emerging studies demonstrate that inflammation plays a crucial role in the patho-genesis of bipolar disorder (BD), but the underlying mechanism remains largely un-clear. Given the complexity of BD pathogenesis, we performed high-throughput multi-omic profiling (metabolomics, lipidomics, and transcriptomics) of the BD ze-brafish 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 neurotrans-mitters serotonin and dopamine in synaptic vesicle recycling. On the other hand, dysregulated metabolism of the membrane lipids sphingomyelin and glycerophos-pholipids altered the synaptic membrane structure and neurotransmitter recep-tors (chrna7, htr1b, drd5b, and gabra1) activity. Our findings revealed that distur-bance 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.

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