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New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data
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 t...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724122/ https://www.ncbi.nlm.nih.gov/pubmed/34992606 http://dx.doi.org/10.3389/fimmu.2021.789647 |
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author | Lai, Jianbo Zhang, Peifen Jiang, Jiajun Mou, Tingting Li, Yifan Xi, Caixi Wu, Lingling Gao, Xingle Zhang, Danhua Chen, Yiqing Huang, Huimin Li, Huijuan Cai, Xin Li, Ming Zheng, Peng Hu, Shaohua |
author_facet | Lai, Jianbo Zhang, Peifen Jiang, Jiajun Mou, Tingting Li, Yifan Xi, Caixi Wu, Lingling Gao, Xingle Zhang, Danhua Chen, Yiqing Huang, Huimin Li, Huijuan Cai, Xin Li, Ming Zheng, Peng Hu, Shaohua |
author_sort | Lai, Jianbo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8724122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87241222022-01-05 New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data Lai, Jianbo Zhang, Peifen Jiang, Jiajun Mou, Tingting Li, Yifan Xi, Caixi Wu, Lingling Gao, Xingle Zhang, Danhua Chen, Yiqing Huang, Huimin Li, Huijuan Cai, Xin Li, Ming Zheng, Peng Hu, Shaohua Front Immunol Immunology 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. Frontiers Media S.A. 2021-12-21 /pmc/articles/PMC8724122/ /pubmed/34992606 http://dx.doi.org/10.3389/fimmu.2021.789647 Text en Copyright © 2021 Lai, Zhang, Jiang, Mou, Li, Xi, Wu, Gao, Zhang, Chen, Huang, Li, Cai, Li, Zheng and Hu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Lai, Jianbo Zhang, Peifen Jiang, Jiajun Mou, Tingting Li, Yifan Xi, Caixi Wu, Lingling Gao, Xingle Zhang, Danhua Chen, Yiqing Huang, Huimin Li, Huijuan Cai, Xin Li, Ming Zheng, Peng Hu, Shaohua New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data |
title | New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data |
title_full | New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data |
title_fullStr | New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data |
title_full_unstemmed | New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data |
title_short | New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data |
title_sort | new evidence of gut microbiota involvement in the neuropathogenesis of bipolar depression by trank1 modulation: joint clinical and animal data |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724122/ https://www.ncbi.nlm.nih.gov/pubmed/34992606 http://dx.doi.org/10.3389/fimmu.2021.789647 |
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