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New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.
- Source :
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Frontiers in immunology [Front Immunol] 2021 Dec 21; Vol. 12, pp. 789647. Date of Electronic Publication: 2021 Dec 21 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- 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 .<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Lai, Zhang, Jiang, Mou, Li, Xi, Wu, Gao, Zhang, Chen, Huang, Li, Cai, Li, Zheng and Hu.)
- Subjects :
- Adolescent
Adult
Animals
Bipolar Disorder blood
Bipolar Disorder microbiology
Bipolar Disorder pathology
Case-Control Studies
Cell Line
Cytokines analysis
Depression blood
Depression microbiology
Depression pathology
Disease Models, Animal
Fecal Microbiota Transplantation
Female
Healthy Volunteers
Hippocampus immunology
Hippocampus metabolism
Hippocampus pathology
Humans
Lipopolysaccharides immunology
Male
Mice
Microglia immunology
Microglia metabolism
Neurons immunology
Neurons metabolism
Prefrontal Cortex immunology
Prefrontal Cortex metabolism
Prefrontal Cortex pathology
Primary Cell Culture
Young Adult
Bipolar Disorder immunology
Brain-Gut Axis immunology
Cytokines metabolism
Depression immunology
Gastrointestinal Microbiome immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34992606
- Full Text :
- https://doi.org/10.3389/fimmu.2021.789647