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5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing

INTRODUCTION: Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation im...

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Autores principales: Yu, Weizhi, Xu, Hong, Xue, Ying, An, Dong, Li, Huairui, Chen, Wei, Yu, Deqin, Sun, Yiping, Ma, Jianmei, Tang, Yiyuan, Xiao, Zhaoyang, Yin, Shengming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840448/
https://www.ncbi.nlm.nih.gov/pubmed/29541541
http://dx.doi.org/10.1002/brb3.929
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author Yu, Weizhi
Xu, Hong
Xue, Ying
An, Dong
Li, Huairui
Chen, Wei
Yu, Deqin
Sun, Yiping
Ma, Jianmei
Tang, Yiyuan
Xiao, Zhaoyang
Yin, Shengming
author_facet Yu, Weizhi
Xu, Hong
Xue, Ying
An, Dong
Li, Huairui
Chen, Wei
Yu, Deqin
Sun, Yiping
Ma, Jianmei
Tang, Yiyuan
Xiao, Zhaoyang
Yin, Shengming
author_sort Yu, Weizhi
collection PubMed
description INTRODUCTION: Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation impacts adenosine deaminase acting on RNA 1 (ADAR1, RNA editing enzyme) and Htr2c RNA editing, leading to aggressive behavior, and explore the effective solutions for the recovery of this behavior. METHODS: We evaluated 21‐day‐old BALB/c mice with and without isolation for aggressive behavior using a resident‐intruder test. Immune‐reactivity and protein expression of ADAR1 (p110) were measured using immunohistochemistry and Western blotting. Htr2c RNA editing was evaluated using pyrosequencing. In addition, the 5‐HT (2C) R antagonist SB243213/5‐HT (2C) R inverse agonist SB206553 was used to treat the isolated mice, and the performance of both treatments on the behavior, ADAR1 (p110) expression, and Htr2c RNA editing in isolated mice was examined. RESULTS: Both the protein expression and immune‐reactivity of ADAR1 (p110) in the amygdala decreased, but the percentage of Htr2c RNA editing at A and B sites of amygdala only showed a moderate increase in isolated BALB/c mice with enhanced aggressive behavior compared to the age‐matched group‐housed BALB/c mice. Additionally, treatment with the 5‐HT (2C) R antagonist SB243213/5‐HT (2C) R inverse agonist SB206553 recovered the enhanced aggressive behavior of isolated mice and returned the protein expression and immune‐reactivity of ADAR1 (p110) back to the normal level. Moreover, compared to the age‐matched isolated mice treated with physiological saline, isolated mice treated with 5‐HT (2C) R inverse agonist SB206553 showed a lower percentage of Htr2c RNA editing at both A and B sites, and the same result occurred in isolated mice treated with 5‐HT (2C) R antagonist SB243213 at B site of Htr2c RNA editing. CONCLUSIONS: The 5‐HT (2C) R antagonist SB243213/5‐HT (2C) R inverse agonist SB206553 recovered increased aggressive behavior of isolated BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing.
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spelling pubmed-58404482018-03-14 5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing Yu, Weizhi Xu, Hong Xue, Ying An, Dong Li, Huairui Chen, Wei Yu, Deqin Sun, Yiping Ma, Jianmei Tang, Yiyuan Xiao, Zhaoyang Yin, Shengming Brain Behav Original Research INTRODUCTION: Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation impacts adenosine deaminase acting on RNA 1 (ADAR1, RNA editing enzyme) and Htr2c RNA editing, leading to aggressive behavior, and explore the effective solutions for the recovery of this behavior. METHODS: We evaluated 21‐day‐old BALB/c mice with and without isolation for aggressive behavior using a resident‐intruder test. Immune‐reactivity and protein expression of ADAR1 (p110) were measured using immunohistochemistry and Western blotting. Htr2c RNA editing was evaluated using pyrosequencing. In addition, the 5‐HT (2C) R antagonist SB243213/5‐HT (2C) R inverse agonist SB206553 was used to treat the isolated mice, and the performance of both treatments on the behavior, ADAR1 (p110) expression, and Htr2c RNA editing in isolated mice was examined. RESULTS: Both the protein expression and immune‐reactivity of ADAR1 (p110) in the amygdala decreased, but the percentage of Htr2c RNA editing at A and B sites of amygdala only showed a moderate increase in isolated BALB/c mice with enhanced aggressive behavior compared to the age‐matched group‐housed BALB/c mice. Additionally, treatment with the 5‐HT (2C) R antagonist SB243213/5‐HT (2C) R inverse agonist SB206553 recovered the enhanced aggressive behavior of isolated mice and returned the protein expression and immune‐reactivity of ADAR1 (p110) back to the normal level. Moreover, compared to the age‐matched isolated mice treated with physiological saline, isolated mice treated with 5‐HT (2C) R inverse agonist SB206553 showed a lower percentage of Htr2c RNA editing at both A and B sites, and the same result occurred in isolated mice treated with 5‐HT (2C) R antagonist SB243213 at B site of Htr2c RNA editing. CONCLUSIONS: The 5‐HT (2C) R antagonist SB243213/5‐HT (2C) R inverse agonist SB206553 recovered increased aggressive behavior of isolated BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing. John Wiley and Sons Inc. 2018-02-07 /pmc/articles/PMC5840448/ /pubmed/29541541 http://dx.doi.org/10.1002/brb3.929 Text en © 2018 National Natural Science Foundation of China and The China Scholarship Council. Brain and Behavior published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Yu, Weizhi
Xu, Hong
Xue, Ying
An, Dong
Li, Huairui
Chen, Wei
Yu, Deqin
Sun, Yiping
Ma, Jianmei
Tang, Yiyuan
Xiao, Zhaoyang
Yin, Shengming
5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing
title 5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing
title_full 5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing
title_fullStr 5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing
title_full_unstemmed 5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing
title_short 5‐HT (2C) R antagonist/5‐HT (2C) R inverse agonist recovered the increased isolation‐induced aggressive behavior of BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing
title_sort 5‐ht (2c) r antagonist/5‐ht (2c) r inverse agonist recovered the increased isolation‐induced aggressive behavior of balb/c mice mediated by adar1 (p110) expression and htr2c rna editing
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840448/
https://www.ncbi.nlm.nih.gov/pubmed/29541541
http://dx.doi.org/10.1002/brb3.929
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