机构：[1]Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,浙江大学医学院附属第一医院[2]The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, China,[3]Brain Research Institute of Zhejiang University, Hangzhou, China,[4]MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, China,[5]Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China,重庆医科大学附属第一医院[6]NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China,重庆医科大学附属第一医院[7]Institute of Psychiatry, Wenzhou Medical University, Wenzhou, China,[8]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring 'BD microbiota' following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.
基金：
This study was granted by the National Natural Science
Foundation of China (81971271), and the Natural Science
Foundation of Zhejiang Province (LQ20H090013).
第一作者机构：[1]Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,[2]The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, China,[3]Brain Research Institute of Zhejiang University, Hangzhou, China,[4]MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, China,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,[2]The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, China,[3]Brain Research Institute of Zhejiang University, Hangzhou, China,[4]MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, China,
推荐引用方式(GB/T 7714)：
Lai Jianbo,Zhang Peifen,Jiang Jiajun,et al.New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data[J].FRONTIERS IN IMMUNOLOGY.2021,12:doi:10.3389/fimmu.2021.789647.
APA：
Lai, Jianbo,Zhang, Peifen,Jiang, Jiajun,Mou, Tingting,Li, Yifan...&Hu, Shaohua.(2021).New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.FRONTIERS IN IMMUNOLOGY,12,
MLA：
Lai, Jianbo,et al."New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data".FRONTIERS IN IMMUNOLOGY 12.(2021)
医学