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Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis

Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on beha...

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Autores principales: Huo, Ran, Zeng, Benhua, Zeng, Li, Cheng, Ke, Li, Bo, Luo, Yuanyuan, Wang, Haiyang, Zhou, Chanjuan, Fang, Liang, Li, Wenxia, Niu, Rong, Wei, Hong, Xie, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715198/
https://www.ncbi.nlm.nih.gov/pubmed/29250490
http://dx.doi.org/10.3389/fcimb.2017.00489
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author Huo, Ran
Zeng, Benhua
Zeng, Li
Cheng, Ke
Li, Bo
Luo, Yuanyuan
Wang, Haiyang
Zhou, Chanjuan
Fang, Liang
Li, Wenxia
Niu, Rong
Wei, Hong
Xie, Peng
author_facet Huo, Ran
Zeng, Benhua
Zeng, Li
Cheng, Ke
Li, Bo
Luo, Yuanyuan
Wang, Haiyang
Zhou, Chanjuan
Fang, Liang
Li, Wenxia
Niu, Rong
Wei, Hong
Xie, Peng
author_sort Huo, Ran
collection PubMed
description Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA) axis under stress. We tested germ-free (GF) mice and specific pathogen-free (SPF) mice, divided into four groups. A chronic restraint stress (CRS) protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases.
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spelling pubmed-57151982017-12-15 Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis Huo, Ran Zeng, Benhua Zeng, Li Cheng, Ke Li, Bo Luo, Yuanyuan Wang, Haiyang Zhou, Chanjuan Fang, Liang Li, Wenxia Niu, Rong Wei, Hong Xie, Peng Front Cell Infect Microbiol Microbiology Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA) axis under stress. We tested germ-free (GF) mice and specific pathogen-free (SPF) mice, divided into four groups. A chronic restraint stress (CRS) protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases. Frontiers Media S.A. 2017-11-30 /pmc/articles/PMC5715198/ /pubmed/29250490 http://dx.doi.org/10.3389/fcimb.2017.00489 Text en Copyright © 2017 Huo, Zeng, Zeng, Cheng, Li, Luo, Wang, Zhou, Fang, Li, Niu, Wei and Xie. http://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) or licensor 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 Microbiology
Huo, Ran
Zeng, Benhua
Zeng, Li
Cheng, Ke
Li, Bo
Luo, Yuanyuan
Wang, Haiyang
Zhou, Chanjuan
Fang, Liang
Li, Wenxia
Niu, Rong
Wei, Hong
Xie, Peng
Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis
title Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis
title_full Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis
title_fullStr Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis
title_full_unstemmed Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis
title_short Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis
title_sort microbiota modulate anxiety-like behavior and endocrine abnormalities in hypothalamic-pituitary-adrenal axis
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715198/
https://www.ncbi.nlm.nih.gov/pubmed/29250490
http://dx.doi.org/10.3389/fcimb.2017.00489
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