Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway
Shuhan Liu,1 Rongjuan Guo,2 Fei Liu,3 Qingjie Yuan,4 Yao Yu,1 Feifei Ren1 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2020-03-01
|
Series: | Neuropsychiatric Disease and Treatment |
Subjects: | |
Online Access: | https://www.dovepress.com/gut-microbiota-regulates-depression-like-behavior-in-rats-through-the--peer-reviewed-article-NDT |
id |
doaj-8f292c705fc34b9ba572b710f46972e2 |
---|---|
record_format |
Article |
spelling |
doaj-8f292c705fc34b9ba572b710f46972e22020-11-25T01:58:16ZengDove Medical PressNeuropsychiatric Disease and Treatment1178-20212020-03-01Volume 1685986952849Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial PathwayLiu SGuo RLiu FYuan QYu YRen FShuhan Liu,1 Rongjuan Guo,2 Fei Liu,3 Qingjie Yuan,4 Yao Yu,1 Feifei Ren1 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China; 3College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China; 4Department of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of ChinaCorrespondence: Rongjuan GuoDepartment of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Fangxingyuan 1st Block, Fengtai District, Beijing City, People’s Republic of ChinaTel +86 1 861 137 7633Fax +86 1064286498Email dfguorongjuan@163.comPurpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.Keywords: gut microbiota, depression, neurotransmitter, HPA axis, immune, mitochondrialhttps://www.dovepress.com/gut-microbiota-regulates-depression-like-behavior-in-rats-through-the--peer-reviewed-article-NDTgut microbiotadepressionneurotransmitterhpa axisimmunemitochondrial |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Liu S Guo R Liu F Yuan Q Yu Y Ren F |
spellingShingle |
Liu S Guo R Liu F Yuan Q Yu Y Ren F Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway Neuropsychiatric Disease and Treatment gut microbiota depression neurotransmitter hpa axis immune mitochondrial |
author_facet |
Liu S Guo R Liu F Yuan Q Yu Y Ren F |
author_sort |
Liu S |
title |
Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway |
title_short |
Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway |
title_full |
Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway |
title_fullStr |
Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway |
title_full_unstemmed |
Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway |
title_sort |
gut microbiota regulates depression-like behavior in rats through the neuroendocrine-immune-mitochondrial pathway |
publisher |
Dove Medical Press |
series |
Neuropsychiatric Disease and Treatment |
issn |
1178-2021 |
publishDate |
2020-03-01 |
description |
Shuhan Liu,1 Rongjuan Guo,2 Fei Liu,3 Qingjie Yuan,4 Yao Yu,1 Feifei Ren1 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China; 3College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China; 4Department of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of ChinaCorrespondence: Rongjuan GuoDepartment of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Fangxingyuan 1st Block, Fengtai District, Beijing City, People’s Republic of ChinaTel +86 1 861 137 7633Fax +86 1064286498Email dfguorongjuan@163.comPurpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.Keywords: gut microbiota, depression, neurotransmitter, HPA axis, immune, mitochondrial |
topic |
gut microbiota depression neurotransmitter hpa axis immune mitochondrial |
url |
https://www.dovepress.com/gut-microbiota-regulates-depression-like-behavior-in-rats-through-the--peer-reviewed-article-NDT |
work_keys_str_mv |
AT lius gutmicrobiotaregulatesdepressionlikebehaviorinratsthroughtheneuroendocrineimmunemitochondrialpathway AT guor gutmicrobiotaregulatesdepressionlikebehaviorinratsthroughtheneuroendocrineimmunemitochondrialpathway AT liuf gutmicrobiotaregulatesdepressionlikebehaviorinratsthroughtheneuroendocrineimmunemitochondrialpathway AT yuanq gutmicrobiotaregulatesdepressionlikebehaviorinratsthroughtheneuroendocrineimmunemitochondrialpathway AT yuy gutmicrobiotaregulatesdepressionlikebehaviorinratsthroughtheneuroendocrineimmunemitochondrialpathway AT renf gutmicrobiotaregulatesdepressionlikebehaviorinratsthroughtheneuroendocrineimmunemitochondrialpathway |
_version_ |
1724970591140708352 |