MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder
Background Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-...
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BMJ Publishing Group
2024-02-01
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| Series: | General Psychiatry |
| Online Access: | https://gpsych.bmj.com/content/37/1/e101291.full |
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| author | Yan Chen Yun Liu Ming Xiao Chun Wang Panpan Hu Qiuchen Cao Hu Feng Jingfan Xu Weixi Feng Huaiqing Sun Huachen Ding Junying Gao |
| author_facet | Yan Chen Yun Liu Ming Xiao Chun Wang Panpan Hu Qiuchen Cao Hu Feng Jingfan Xu Weixi Feng Huaiqing Sun Huachen Ding Junying Gao |
| author_sort | Yan Chen |
| collection | DOAJ |
| description | Background Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress (CRS). Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex (mPFC) via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses. Finally, molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451a were significantly lower in patients with MDD, with a negative correlation with the Hamilton Depression Scale scores. Additionally, a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice. Notably, miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice. Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice. Mechanistically, miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2, subsequently protecting dendritic spine plasticity.Conclusions Together, these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD. |
| format | Article |
| id | doaj-art-aff1154fc0ea44549a21e17d9103c420 |
| institution | Kabale University |
| issn | 2517-729X |
| language | English |
| publishDate | 2024-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | General Psychiatry |
| spelling | doaj-art-aff1154fc0ea44549a21e17d9103c4202025-01-29T16:50:11ZengBMJ Publishing GroupGeneral Psychiatry2517-729X2024-02-0137110.1136/gpsych-2023-101291MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorderYan Chen0Yun Liu1Ming Xiao2Chun Wang3Panpan Hu4Qiuchen Cao5Hu Feng6Jingfan Xu7Weixi Feng8Huaiqing Sun9Huachen Ding10Junying Gao111 Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China1 Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu, China4 Functional Brain Imaging Institute of Nanjing Medical University, Nanjing, Jiangsu, ChinaPeking University Shenzhen Hospital, Shenzhen, 518036, China1 Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China1 Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China1 Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China1 Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China1 Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China2 Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China3 Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China1 Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, ChinaBackground Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress (CRS). Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex (mPFC) via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses. Finally, molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451a were significantly lower in patients with MDD, with a negative correlation with the Hamilton Depression Scale scores. Additionally, a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice. Notably, miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice. Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice. Mechanistically, miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2, subsequently protecting dendritic spine plasticity.Conclusions Together, these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.https://gpsych.bmj.com/content/37/1/e101291.full |
| spellingShingle | Yan Chen Yun Liu Ming Xiao Chun Wang Panpan Hu Qiuchen Cao Hu Feng Jingfan Xu Weixi Feng Huaiqing Sun Huachen Ding Junying Gao MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder General Psychiatry |
| title | MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder |
| title_full | MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder |
| title_fullStr | MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder |
| title_full_unstemmed | MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder |
| title_short | MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder |
| title_sort | microrna 451a is a candidate biomarker and therapeutic target for major depressive disorder |
| url | https://gpsych.bmj.com/content/37/1/e101291.full |
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