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

Weizhi Yu; Hong Xu; Ying Xue; Dong An; Huairui Li; Wei Chen; Deqin Yu; Yiping Sun; Jianmei Ma; Yiyuan Tang; Zhaoyang Xiao; Shengming Yin

doi:10.1002/brb3.929

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

Weizhi Yu, Hong Xu, Ying Xue, Dong An, Huairui Li, Wei Chen, Deqin Yu, Yiping Sun, Jianmei Ma, Yiyuan Tang, Zhaoyang Xiao, Shengming Yin

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e00929
Journal	Brain and Behavior
Volume	8
Issue number	3
DOIs	https://doi.org/10.1002/brb3.929
State	Published - Mar 2018
Externally published	Yes

Keywords

5-HT R
ADAR1
aggressive behavior

ASJC Scopus subject areas

Behavioral Neuroscience

Access to Document

10.1002/brb3.929

Cite this

Yu, W., Xu, H., Xue, Y., An, D., Li, H., Chen, W., Yu, D., Sun, Y., Ma, J., Tang, Y., Xiao, Z., & Yin, S. (2018). 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 Brain and Behavior, 8(3), Article e00929. https://doi.org/10.1002/brb3.929

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 et al.
In: Brain and Behavior, Vol. 8, No. 3, e00929, 03.2018.

Research output: Contribution to journal › Article › peer-review

Yu, W, Xu, H, Xue, Y, An, D, Li, H, Chen, W, Yu, D, Sun, Y, Ma, J, Tang, Y, Xiao, Z & Yin, S 2018, ' 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 ', Brain and Behavior, vol. 8, no. 3, e00929. https://doi.org/10.1002/brb3.929

Yu W, Xu H, Xue Y, An D, Li H, Chen W et al. 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 Brain and Behavior. 2018 Mar;8(3):e00929. doi: 10.1002/brb3.929

Yu, Weizhi ; Xu, Hong ; Xue, Ying et al. / 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 In: Brain and Behavior. 2018 ; Vol. 8, No. 3.

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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 ",

abstract = " 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.",

keywords = "5-HT R, ADAR1, aggressive behavior",

author = "Weizhi Yu and Hong Xu and Ying Xue and Dong An and Huairui Li and Wei Chen and Deqin Yu and Yiping Sun and Jianmei Ma and Yiyuan Tang and Zhaoyang Xiao and Shengming Yin",

note = "Funding Information: College Students{\textquoteright} Scientific Research Innovation Activities of Liaoning Province (Grant/Award Number: {\textquoteleft}201310161008{\textquoteleft}), China Scholarship Council (Grant/Award Number: {\textquoteleft}201408210227{\textquoteleft}), National Natural Science Foundation of China (Grant/Award Number: {\textquoteleft}31201724{\textquoteleft}, {\textquoteleft}81471373{\textquoteleft}) Funding Information: Funding information College Students? Scientific Research Innovation Activities of Liaoning Province (Grant/Award Number: ?201310161008?), China Scholarship Council (Grant/Award Number: ?201408210227?), National Natural Science Foundation of China (Grant/Award Number: ?31201724?, ?81471373?) This study was financially supported by grants from the National Natural Science Foundation of China (31201724 and 81471373) and the China Scholarship Council (201408210227). The authors would like to thank Dr. Song Li for technical support. Funding Information: This study was financially supported by grants from the National Natural Science Foundation of China (31201724 and 81471373) and the China Scholarship Council (201408210227). The authors would like to thank Dr. Song Li for technical support. Publisher Copyright: {\textcopyright} 2018 National Natural Science Foundation of China and The China Scholarship Council. Brain and Behavior published by Wiley Periodicals, Inc.",

year = "2018",

month = mar,

doi = "10.1002/brb3.929",

language = "English (US)",

volume = "8",

journal = "Brain and Behavior",

issn = "2157-9032",

publisher = "John Wiley and Sons Inc.",

number = "3",

}

TY - JOUR

T1 - 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

AU - Yu, Weizhi

AU - Xu, Hong

AU - Xue, Ying

AU - An, Dong

AU - Li, Huairui

AU - Chen, Wei

AU - Yu, Deqin

AU - Sun, Yiping

AU - Ma, Jianmei

AU - Tang, Yiyuan

AU - Xiao, Zhaoyang

AU - Yin, Shengming

N1 - Funding Information: College Students’ Scientific Research Innovation Activities of Liaoning Province (Grant/Award Number: ‘201310161008‘), China Scholarship Council (Grant/Award Number: ‘201408210227‘), National Natural Science Foundation of China (Grant/Award Number: ‘31201724‘, ‘81471373‘) Funding Information: Funding information College Students? Scientific Research Innovation Activities of Liaoning Province (Grant/Award Number: ?201310161008?), China Scholarship Council (Grant/Award Number: ?201408210227?), National Natural Science Foundation of China (Grant/Award Number: ?31201724?, ?81471373?) This study was financially supported by grants from the National Natural Science Foundation of China (31201724 and 81471373) and the China Scholarship Council (201408210227). The authors would like to thank Dr. Song Li for technical support. Funding Information: This study was financially supported by grants from the National Natural Science Foundation of China (31201724 and 81471373) and the China Scholarship Council (201408210227). The authors would like to thank Dr. Song Li for technical support. Publisher Copyright: © 2018 National Natural Science Foundation of China and The China Scholarship Council. Brain and Behavior published by Wiley Periodicals, Inc.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - 5-HT R

KW - ADAR1

KW - aggressive behavior

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