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Attractin Participates in Schizophrenia by Affecting Testosterone Levels

Attractin (ATRN) is a widely expressed glycoprotein that is involved in energy homeostasis, neurodevelopment, and immune response. It is encoded by a gene spanning 180 kb on chromosome 20p13, a region previously implicated in schizophrenia by linkage studies. To address a possible role of ATRN in di...

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Autores principales: Li, Nan, Gao, Shuzhan, Wang, Shuang, He, Sijie, Wang, Jiayin, He, Luqingqing, Jiang, Dongya, Shi, Yun Stone, Zhang, Jianguo, Gu, Yuan, Chen, Tian, Kong, Mingjun, Xu, Xijia, Zhao, Qingshun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636034/
https://www.ncbi.nlm.nih.gov/pubmed/34869343
http://dx.doi.org/10.3389/fcell.2021.755165
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author Li, Nan
Gao, Shuzhan
Wang, Shuang
He, Sijie
Wang, Jiayin
He, Luqingqing
Jiang, Dongya
Shi, Yun Stone
Zhang, Jianguo
Gu, Yuan
Chen, Tian
Kong, Mingjun
Xu, Xijia
Zhao, Qingshun
author_facet Li, Nan
Gao, Shuzhan
Wang, Shuang
He, Sijie
Wang, Jiayin
He, Luqingqing
Jiang, Dongya
Shi, Yun Stone
Zhang, Jianguo
Gu, Yuan
Chen, Tian
Kong, Mingjun
Xu, Xijia
Zhao, Qingshun
author_sort Li, Nan
collection PubMed
description Attractin (ATRN) is a widely expressed glycoprotein that is involved in energy homeostasis, neurodevelopment, and immune response. It is encoded by a gene spanning 180 kb on chromosome 20p13, a region previously implicated in schizophrenia by linkage studies. To address a possible role of ATRN in disorders of the central nervous system, we created an atrn knockout zebrafish line and performed behavioral tests. Adult atrn(–/–) zebrafish exhibited more pronounced attack behavior relative to wild-type control zebrafish in a tracking analysis. Biochemical analysis revealed elevated testosterone levels in atrn(–/–) zebrafish. At the gene expression level, we noted an upregulation of cyp51 and hsd17b7, key proteins in testosterone synthesis in the brains of both adult and larvae of atrn(–/–) zebrafish. In order to further elucidate the relationship between testosterone and behavioral syndromes, we then compared testosterone levels of 9,008 psychiatric patients and 247 healthy controls from the same catchment area. Of all subjects examined, male subjects with schizophrenia exhibited lower testosterone levels compared with controls. In contrast, female subjects with a diagnosis of schizophrenia or bipolar disorder featured higher testosterone levels than did same sex controls. Purposeful sampling of extreme groups showed reduced ATRN expression in a subset of these subjects. Finally, we identified 14 subjects with ATRN mutations. All of whom displayed abnormal testosterone levels. In summary, the interplay of ATRN and testosterone may help to explain sexual dimorphisms in selected behavioral phenotypes.
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spelling pubmed-86360342021-12-02 Attractin Participates in Schizophrenia by Affecting Testosterone Levels Li, Nan Gao, Shuzhan Wang, Shuang He, Sijie Wang, Jiayin He, Luqingqing Jiang, Dongya Shi, Yun Stone Zhang, Jianguo Gu, Yuan Chen, Tian Kong, Mingjun Xu, Xijia Zhao, Qingshun Front Cell Dev Biol Cell and Developmental Biology Attractin (ATRN) is a widely expressed glycoprotein that is involved in energy homeostasis, neurodevelopment, and immune response. It is encoded by a gene spanning 180 kb on chromosome 20p13, a region previously implicated in schizophrenia by linkage studies. To address a possible role of ATRN in disorders of the central nervous system, we created an atrn knockout zebrafish line and performed behavioral tests. Adult atrn(–/–) zebrafish exhibited more pronounced attack behavior relative to wild-type control zebrafish in a tracking analysis. Biochemical analysis revealed elevated testosterone levels in atrn(–/–) zebrafish. At the gene expression level, we noted an upregulation of cyp51 and hsd17b7, key proteins in testosterone synthesis in the brains of both adult and larvae of atrn(–/–) zebrafish. In order to further elucidate the relationship between testosterone and behavioral syndromes, we then compared testosterone levels of 9,008 psychiatric patients and 247 healthy controls from the same catchment area. Of all subjects examined, male subjects with schizophrenia exhibited lower testosterone levels compared with controls. In contrast, female subjects with a diagnosis of schizophrenia or bipolar disorder featured higher testosterone levels than did same sex controls. Purposeful sampling of extreme groups showed reduced ATRN expression in a subset of these subjects. Finally, we identified 14 subjects with ATRN mutations. All of whom displayed abnormal testosterone levels. In summary, the interplay of ATRN and testosterone may help to explain sexual dimorphisms in selected behavioral phenotypes. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8636034/ /pubmed/34869343 http://dx.doi.org/10.3389/fcell.2021.755165 Text en Copyright © 2021 Li, Gao, Wang, He, Wang, He, Jiang, Shi, Zhang, Gu, Chen, Kong, Xu and Zhao. 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 Cell and Developmental Biology
Li, Nan
Gao, Shuzhan
Wang, Shuang
He, Sijie
Wang, Jiayin
He, Luqingqing
Jiang, Dongya
Shi, Yun Stone
Zhang, Jianguo
Gu, Yuan
Chen, Tian
Kong, Mingjun
Xu, Xijia
Zhao, Qingshun
Attractin Participates in Schizophrenia by Affecting Testosterone Levels
title Attractin Participates in Schizophrenia by Affecting Testosterone Levels
title_full Attractin Participates in Schizophrenia by Affecting Testosterone Levels
title_fullStr Attractin Participates in Schizophrenia by Affecting Testosterone Levels
title_full_unstemmed Attractin Participates in Schizophrenia by Affecting Testosterone Levels
title_short Attractin Participates in Schizophrenia by Affecting Testosterone Levels
title_sort attractin participates in schizophrenia by affecting testosterone levels
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636034/
https://www.ncbi.nlm.nih.gov/pubmed/34869343
http://dx.doi.org/10.3389/fcell.2021.755165
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