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

被引：9

作者：

Li, Yameng ^{[1
]}

Zhang, Lin ^{[1
]}

Mao, Mingcai ^{[1
]}

He, Linjuan ^{[1
]}

Wang, Tiancai ^{[1
]}

Pan, Yecan ^{[1
]}

Zhao, Xiaoyu ^{[1
]}

Li, Zishu ^{[1
]}

Mu, Xiyan ^{[1
]}

Qian, Yongzhong ^{[1
]}

Qiu, Jing ^{[1
]}

机构：

[1] Inst Qual Stand & Testing Technol Agroprod, Chinese Acad Agr Sci, Key Lab Agrifood Qual & Safety, Minist Agr & Rural Affairs, Beijing 100081, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 05期

关键词：

MITOCHONDRIAL DYSFUNCTION; MENTAL-HEALTH; METABOLISM;

D O I：

10.1016/j.isci.2023.106744

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页数：25

共 81 条

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