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Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission
Schizophrenia is a polygenetic disease, the heterogeneity of which is likely complicated by epigenetic modifications yet to be elucidated. Here, we performed transcriptomic analysis of peripheral blood RNA from monozygotic twins discordant for schizophrenia and identified a schizophrenia-associated...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9390987/ https://www.ncbi.nlm.nih.gov/pubmed/35984881 http://dx.doi.org/10.1126/sciadv.abn7357 |
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author | Liang, Wenquan Hou, Yu Huang, Weiyuan Wang, Yunqian Jiang, Tingyun Huang, Xingbing Wang, Zhongju Wu, Fengchun Zheng, Jiawei Zhang, Jie Ou, Haiyan Li, Shuyun Ping, Junjiao Zhang, Yuan Ye, Junping Li, Zhongwei Yang, Qiong Zhang, Jian Zheng, Xianzhen Li, Shufen Zhu, Xin-Hong Chen, Rongqing Zhao, Cunyou |
author_facet | Liang, Wenquan Hou, Yu Huang, Weiyuan Wang, Yunqian Jiang, Tingyun Huang, Xingbing Wang, Zhongju Wu, Fengchun Zheng, Jiawei Zhang, Jie Ou, Haiyan Li, Shuyun Ping, Junjiao Zhang, Yuan Ye, Junping Li, Zhongwei Yang, Qiong Zhang, Jian Zheng, Xianzhen Li, Shufen Zhu, Xin-Hong Chen, Rongqing Zhao, Cunyou |
author_sort | Liang, Wenquan |
collection | PubMed |
description | Schizophrenia is a polygenetic disease, the heterogeneity of which is likely complicated by epigenetic modifications yet to be elucidated. Here, we performed transcriptomic analysis of peripheral blood RNA from monozygotic twins discordant for schizophrenia and identified a schizophrenia-associated down-regulated microRNA, miR-501-3p. We showed that the loss of miR-501-3p in germline knockout (KO) male mice resulted in dendritic structure defects, glutamatergic transmission enhancement, and sociability, memory, and sensorimotor gating disruptions, which were attenuated when miR-501 expression was conditionally restored in the nervous system. Combining the results of proteomic analyses with the known genes linked to schizophrenia revealed that metabotropic glutamate receptor 5 (mGluR5) was one of the miR-501-3p targets and was elevated in vivo upon loss of miR-501. Treatment with the mGluR5 negative allosteric modulator 3-2((-methyl-4-thiazolyl) ethynyl) pyridine or the N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid ameliorated the deficits observed in Mir501-KO mice. The epigenetic and pathophysiological mechanism that links miR-501-3p to the modulation of glutamatergic transmission provides etiological implications for schizophrenia. |
format | Online Article Text |
id | pubmed-9390987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-93909872022-08-26 Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission Liang, Wenquan Hou, Yu Huang, Weiyuan Wang, Yunqian Jiang, Tingyun Huang, Xingbing Wang, Zhongju Wu, Fengchun Zheng, Jiawei Zhang, Jie Ou, Haiyan Li, Shuyun Ping, Junjiao Zhang, Yuan Ye, Junping Li, Zhongwei Yang, Qiong Zhang, Jian Zheng, Xianzhen Li, Shufen Zhu, Xin-Hong Chen, Rongqing Zhao, Cunyou Sci Adv Neuroscience Schizophrenia is a polygenetic disease, the heterogeneity of which is likely complicated by epigenetic modifications yet to be elucidated. Here, we performed transcriptomic analysis of peripheral blood RNA from monozygotic twins discordant for schizophrenia and identified a schizophrenia-associated down-regulated microRNA, miR-501-3p. We showed that the loss of miR-501-3p in germline knockout (KO) male mice resulted in dendritic structure defects, glutamatergic transmission enhancement, and sociability, memory, and sensorimotor gating disruptions, which were attenuated when miR-501 expression was conditionally restored in the nervous system. Combining the results of proteomic analyses with the known genes linked to schizophrenia revealed that metabotropic glutamate receptor 5 (mGluR5) was one of the miR-501-3p targets and was elevated in vivo upon loss of miR-501. Treatment with the mGluR5 negative allosteric modulator 3-2((-methyl-4-thiazolyl) ethynyl) pyridine or the N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid ameliorated the deficits observed in Mir501-KO mice. The epigenetic and pathophysiological mechanism that links miR-501-3p to the modulation of glutamatergic transmission provides etiological implications for schizophrenia. American Association for the Advancement of Science 2022-08-19 /pmc/articles/PMC9390987/ /pubmed/35984881 http://dx.doi.org/10.1126/sciadv.abn7357 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Neuroscience Liang, Wenquan Hou, Yu Huang, Weiyuan Wang, Yunqian Jiang, Tingyun Huang, Xingbing Wang, Zhongju Wu, Fengchun Zheng, Jiawei Zhang, Jie Ou, Haiyan Li, Shuyun Ping, Junjiao Zhang, Yuan Ye, Junping Li, Zhongwei Yang, Qiong Zhang, Jian Zheng, Xianzhen Li, Shufen Zhu, Xin-Hong Chen, Rongqing Zhao, Cunyou Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission |
title | Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission |
title_full | Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission |
title_fullStr | Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission |
title_full_unstemmed | Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission |
title_short | Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission |
title_sort | loss of schizophrenia-related mir-501-3p in mice impairs sociability and memory by enhancing mglur5-mediated glutamatergic transmission |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9390987/ https://www.ncbi.nlm.nih.gov/pubmed/35984881 http://dx.doi.org/10.1126/sciadv.abn7357 |
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