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A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury
Traumatic brain injury (TBI) can lead to different neurological and psychiatric disorders. Circular RNAs (circRNAs) are highly expressed in the nervous system and enriched in synapses; yet, the underlying role and mechanisms of circRNAs in neurological impairment and dysfunction are still not fully...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734054/ https://www.ncbi.nlm.nih.gov/pubmed/35918398 http://dx.doi.org/10.1038/s41380-022-01711-7 |
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author | Du, Mengran Wu, Chenrui Yu, Renqiang Cheng, Yuqi Tang, Zhaohua Wu, Biying Fu, Jiayuanyuan Tan, Weilin Zhou, Qiang Zhu, Ziyu Balawi, Ehab Huang, Xuekang Ma, Jun Liao, Z. B. |
author_facet | Du, Mengran Wu, Chenrui Yu, Renqiang Cheng, Yuqi Tang, Zhaohua Wu, Biying Fu, Jiayuanyuan Tan, Weilin Zhou, Qiang Zhu, Ziyu Balawi, Ehab Huang, Xuekang Ma, Jun Liao, Z. B. |
author_sort | Du, Mengran |
collection | PubMed |
description | Traumatic brain injury (TBI) can lead to different neurological and psychiatric disorders. Circular RNAs (circRNAs) are highly expressed in the nervous system and enriched in synapses; yet, the underlying role and mechanisms of circRNAs in neurological impairment and dysfunction are still not fully understood. In this study, we investigated the expression of circRNAs and their relation with neurological dysfunction after TBI. RNA-Seq was used to detect differentially expressed circRNAs in injured brain tissue, revealing that circIgfbp2 was significantly increased. Up-regulated hsa_circ_0058195, which was highly homologous to circIgfbp2, was further confirmed in the cerebral cortex specimens and serum samples of patients after TBI. Moreover, correlation analysis showed a positive correlation between hsa_circ_0058195 levels and the Self-Rating Anxiety Scale scores in these subjects. Furthermore, knockdown of circIgfbp2 in mice relieved anxiety-like behaviors and sleep disturbances induced by TBI. Knockdown of circIgfbp2 in H(2)O(2) treated HT22 cells alleviated mitochondrial dysfunction, while its overexpression reversed the process. Mechanistically, we discovered that circIgfbp2 targets miR-370-3p to regulate BACH1, and down-regulating BACH1 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction. In conclusion, inhibition of circIgfbp2 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after TBI through the miR-370-3p/BACH1/HO-1 axis. Thus, circIgfbp2 might be a novel therapeutic target for anxiety and sleep disorders after TBI. |
format | Online Article Text |
id | pubmed-9734054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97340542022-12-11 A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury Du, Mengran Wu, Chenrui Yu, Renqiang Cheng, Yuqi Tang, Zhaohua Wu, Biying Fu, Jiayuanyuan Tan, Weilin Zhou, Qiang Zhu, Ziyu Balawi, Ehab Huang, Xuekang Ma, Jun Liao, Z. B. Mol Psychiatry Article Traumatic brain injury (TBI) can lead to different neurological and psychiatric disorders. Circular RNAs (circRNAs) are highly expressed in the nervous system and enriched in synapses; yet, the underlying role and mechanisms of circRNAs in neurological impairment and dysfunction are still not fully understood. In this study, we investigated the expression of circRNAs and their relation with neurological dysfunction after TBI. RNA-Seq was used to detect differentially expressed circRNAs in injured brain tissue, revealing that circIgfbp2 was significantly increased. Up-regulated hsa_circ_0058195, which was highly homologous to circIgfbp2, was further confirmed in the cerebral cortex specimens and serum samples of patients after TBI. Moreover, correlation analysis showed a positive correlation between hsa_circ_0058195 levels and the Self-Rating Anxiety Scale scores in these subjects. Furthermore, knockdown of circIgfbp2 in mice relieved anxiety-like behaviors and sleep disturbances induced by TBI. Knockdown of circIgfbp2 in H(2)O(2) treated HT22 cells alleviated mitochondrial dysfunction, while its overexpression reversed the process. Mechanistically, we discovered that circIgfbp2 targets miR-370-3p to regulate BACH1, and down-regulating BACH1 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction. In conclusion, inhibition of circIgfbp2 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after TBI through the miR-370-3p/BACH1/HO-1 axis. Thus, circIgfbp2 might be a novel therapeutic target for anxiety and sleep disorders after TBI. Nature Publishing Group UK 2022-08-02 2022 /pmc/articles/PMC9734054/ /pubmed/35918398 http://dx.doi.org/10.1038/s41380-022-01711-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Du, Mengran Wu, Chenrui Yu, Renqiang Cheng, Yuqi Tang, Zhaohua Wu, Biying Fu, Jiayuanyuan Tan, Weilin Zhou, Qiang Zhu, Ziyu Balawi, Ehab Huang, Xuekang Ma, Jun Liao, Z. B. A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury |
title | A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury |
title_full | A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury |
title_fullStr | A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury |
title_full_unstemmed | A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury |
title_short | A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury |
title_sort | novel circular rna, circigfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734054/ https://www.ncbi.nlm.nih.gov/pubmed/35918398 http://dx.doi.org/10.1038/s41380-022-01711-7 |
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