{"title":"EZH2/microRNA-15a-5p/CXCL10轴在抑郁样行为大鼠中的保护机制","authors":"Xuezhu Huang , Chuang Yang , Min Huang","doi":"10.1016/j.jchemneu.2023.102283","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p><span>Enhancer of zeste homolog 2 (EZH2), microRNA-15a-5p (miR-15a-5p), and </span>chemokine<span> C-X-C ligand 10 (CXCL10) have been studied in many diseases. However, the investigation of the EZH2/miR-15a-5p/CXCL10 axis in depression is not sufficient. Our study aimed to investigate the regulatory functions of the EZH2/miR-15a-5p/CXCL10 axis in rats with depressive-like behaviors.</span></p></div><div><h3>Methods</h3><p><span>The rat model of depression-like behaviors was established by chronic unpredictable mild stress (CUMS), and EZH2, miR-15a-5p, and CXCL10 expression levels in rats with depression-like behaviors were detected. The silenced EZH2 or enhanced miR-15a-5p recombinant lentivirus<span> was injected into the rats with depression-like behaviors to assess the changes in behavioral tests, hippocampal pathological structure, levels of inflammatory cytokines in the hippocampus, and hippocampal </span></span>neuron apoptosis. The regulatory relationships among EZH2, miR-15a-5p, and CXCL10 were measured.</p></div><div><h3>Results</h3><p>miR-15a-5p expression was reduced, and EZH2 and CXCL10 expression levels were elevated in rats with depressive-like behaviors. Downregulation of EZH2 or elevation of miR-15a-5p improved depressive behavior, and inhibited hippocampal inflammatory response and hippocampal neuron apoptosis. EZH2 promoted histone methylation at the promoter of miR-15a-5p, and miR-15a-5p bound to CXCL10 to inhibit its expression.</p></div><div><h3>Conclusion</h3><p>Our study summarizes that EZH2 promotes the hypermethylation of the miR-15a-5p promoter, thereby promoting CXCL10 expression. Upregulation of miR-15a-5p or inhibition of EZH2 can improve the symptoms in rats with depressive-like behaviors.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"132 ","pages":"Article 102283"},"PeriodicalIF":2.7000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective mechanism of the EZH2/microRNA-15a-5p/CXCL10 axis in rats with depressive-like behaviors\",\"authors\":\"Xuezhu Huang , Chuang Yang , Min Huang\",\"doi\":\"10.1016/j.jchemneu.2023.102283\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p><span>Enhancer of zeste homolog 2 (EZH2), microRNA-15a-5p (miR-15a-5p), and </span>chemokine<span> C-X-C ligand 10 (CXCL10) have been studied in many diseases. However, the investigation of the EZH2/miR-15a-5p/CXCL10 axis in depression is not sufficient. Our study aimed to investigate the regulatory functions of the EZH2/miR-15a-5p/CXCL10 axis in rats with depressive-like behaviors.</span></p></div><div><h3>Methods</h3><p><span>The rat model of depression-like behaviors was established by chronic unpredictable mild stress (CUMS), and EZH2, miR-15a-5p, and CXCL10 expression levels in rats with depression-like behaviors were detected. The silenced EZH2 or enhanced miR-15a-5p recombinant lentivirus<span> was injected into the rats with depression-like behaviors to assess the changes in behavioral tests, hippocampal pathological structure, levels of inflammatory cytokines in the hippocampus, and hippocampal </span></span>neuron apoptosis. The regulatory relationships among EZH2, miR-15a-5p, and CXCL10 were measured.</p></div><div><h3>Results</h3><p>miR-15a-5p expression was reduced, and EZH2 and CXCL10 expression levels were elevated in rats with depressive-like behaviors. Downregulation of EZH2 or elevation of miR-15a-5p improved depressive behavior, and inhibited hippocampal inflammatory response and hippocampal neuron apoptosis. EZH2 promoted histone methylation at the promoter of miR-15a-5p, and miR-15a-5p bound to CXCL10 to inhibit its expression.</p></div><div><h3>Conclusion</h3><p>Our study summarizes that EZH2 promotes the hypermethylation of the miR-15a-5p promoter, thereby promoting CXCL10 expression. Upregulation of miR-15a-5p or inhibition of EZH2 can improve the symptoms in rats with depressive-like behaviors.</p></div>\",\"PeriodicalId\":15324,\"journal\":{\"name\":\"Journal of chemical neuroanatomy\",\"volume\":\"132 \",\"pages\":\"Article 102283\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of chemical neuroanatomy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0891061823000534\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of chemical neuroanatomy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891061823000534","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Protective mechanism of the EZH2/microRNA-15a-5p/CXCL10 axis in rats with depressive-like behaviors
Objective
Enhancer of zeste homolog 2 (EZH2), microRNA-15a-5p (miR-15a-5p), and chemokine C-X-C ligand 10 (CXCL10) have been studied in many diseases. However, the investigation of the EZH2/miR-15a-5p/CXCL10 axis in depression is not sufficient. Our study aimed to investigate the regulatory functions of the EZH2/miR-15a-5p/CXCL10 axis in rats with depressive-like behaviors.
Methods
The rat model of depression-like behaviors was established by chronic unpredictable mild stress (CUMS), and EZH2, miR-15a-5p, and CXCL10 expression levels in rats with depression-like behaviors were detected. The silenced EZH2 or enhanced miR-15a-5p recombinant lentivirus was injected into the rats with depression-like behaviors to assess the changes in behavioral tests, hippocampal pathological structure, levels of inflammatory cytokines in the hippocampus, and hippocampal neuron apoptosis. The regulatory relationships among EZH2, miR-15a-5p, and CXCL10 were measured.
Results
miR-15a-5p expression was reduced, and EZH2 and CXCL10 expression levels were elevated in rats with depressive-like behaviors. Downregulation of EZH2 or elevation of miR-15a-5p improved depressive behavior, and inhibited hippocampal inflammatory response and hippocampal neuron apoptosis. EZH2 promoted histone methylation at the promoter of miR-15a-5p, and miR-15a-5p bound to CXCL10 to inhibit its expression.
Conclusion
Our study summarizes that EZH2 promotes the hypermethylation of the miR-15a-5p promoter, thereby promoting CXCL10 expression. Upregulation of miR-15a-5p or inhibition of EZH2 can improve the symptoms in rats with depressive-like behaviors.
期刊介绍：
The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches.
Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples.
The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
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