{"title":"由 SIRT1 下调介导的海马突触可塑性损伤与慢性疼痛相关的认知功能障碍有关","authors":"Yanping Liu, Qiang Liu, Haibi Wang, Yongkang Qiu, Jiatao Lin, Weifeng Wu, Ning Wang, Wei Dong, Jie Wan, Chen Chen, Shuai Li, Hui Zheng, Yuqing Wu","doi":"10.1111/cns.14410","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>Cognitive dysfunction associated with chronic pain may be caused by impaired synaptic plasticity. Considering the impact of silent information regulator 1 (SIRT1) on synaptic plasticity, we explored the exact role of SIRT1 in cognitive impairment caused by chronic pain.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We evaluated the memory ability of mice with the fear conditioning test (FCT) after spared nerve injury (SNI) model. Western blotting and immunofluorescence were used to analyze the expression levels of SIRT1. Hippocampal synaptic plasticity was detected with Golgi staining, transmission electron microscopy, and long-term potentiation (LTP). In the intervention study, AAV9-CaMKIIα-Cre-EGFP was injected to SIRT1<sup>flox/flox</sup> mice to knockdown the expression levels of SIRT1. Besides, SNI mice were injected with AAV2/9-CaMKIIα-SIRT1-3*Flag-GFP or SRT1720 to increase the expression levels or enzymatic activity of SIRT1.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Our current results indicated that cognitive function in SNI mice was impaired, SIRT1 expression in glutaminergic neurons in the hippocampal CA1 area was downregulated, and synaptic plasticity was altered. Selective knockdown of SIRT1 in hippocampus damaged synaptic plasticity and cognitive function of healthy mice. In addition, the impaired synaptic plasticity and cognitive dysfunction of SNI mice could be improved by the upregulation of SIRT1 expression or enzyme activity.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Reduced SIRT1 expression in hippocampus of SNI mice may induce cognitive impairment associated with chronic pain by mediating the impaired synaptic plasticity.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 2","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14410","citationCount":"0","resultStr":"{\"title\":\"Hippocampal synaptic plasticity injury mediated by SIRT1 downregulation is involved in chronic pain-related cognitive dysfunction\",\"authors\":\"Yanping Liu, Qiang Liu, Haibi Wang, Yongkang Qiu, Jiatao Lin, Weifeng Wu, Ning Wang, Wei Dong, Jie Wan, Chen Chen, Shuai Li, Hui Zheng, Yuqing Wu\",\"doi\":\"10.1111/cns.14410\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Cognitive dysfunction associated with chronic pain may be caused by impaired synaptic plasticity. Considering the impact of silent information regulator 1 (SIRT1) on synaptic plasticity, we explored the exact role of SIRT1 in cognitive impairment caused by chronic pain.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We evaluated the memory ability of mice with the fear conditioning test (FCT) after spared nerve injury (SNI) model. Western blotting and immunofluorescence were used to analyze the expression levels of SIRT1. Hippocampal synaptic plasticity was detected with Golgi staining, transmission electron microscopy, and long-term potentiation (LTP). In the intervention study, AAV9-CaMKIIα-Cre-EGFP was injected to SIRT1<sup>flox/flox</sup> mice to knockdown the expression levels of SIRT1. Besides, SNI mice were injected with AAV2/9-CaMKIIα-SIRT1-3*Flag-GFP or SRT1720 to increase the expression levels or enzymatic activity of SIRT1.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Our current results indicated that cognitive function in SNI mice was impaired, SIRT1 expression in glutaminergic neurons in the hippocampal CA1 area was downregulated, and synaptic plasticity was altered. Selective knockdown of SIRT1 in hippocampus damaged synaptic plasticity and cognitive function of healthy mice. In addition, the impaired synaptic plasticity and cognitive dysfunction of SNI mice could be improved by the upregulation of SIRT1 expression or enzyme activity.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Reduced SIRT1 expression in hippocampus of SNI mice may induce cognitive impairment associated with chronic pain by mediating the impaired synaptic plasticity.</p>\\n </section>\\n </div>\",\"PeriodicalId\":154,\"journal\":{\"name\":\"CNS Neuroscience & Therapeutics\",\"volume\":\"30 2\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2023-08-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.14410\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS Neuroscience & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cns.14410\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.14410","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Hippocampal synaptic plasticity injury mediated by SIRT1 downregulation is involved in chronic pain-related cognitive dysfunction
Aims
Cognitive dysfunction associated with chronic pain may be caused by impaired synaptic plasticity. Considering the impact of silent information regulator 1 (SIRT1) on synaptic plasticity, we explored the exact role of SIRT1 in cognitive impairment caused by chronic pain.
Methods
We evaluated the memory ability of mice with the fear conditioning test (FCT) after spared nerve injury (SNI) model. Western blotting and immunofluorescence were used to analyze the expression levels of SIRT1. Hippocampal synaptic plasticity was detected with Golgi staining, transmission electron microscopy, and long-term potentiation (LTP). In the intervention study, AAV9-CaMKIIα-Cre-EGFP was injected to SIRT1flox/flox mice to knockdown the expression levels of SIRT1. Besides, SNI mice were injected with AAV2/9-CaMKIIα-SIRT1-3*Flag-GFP or SRT1720 to increase the expression levels or enzymatic activity of SIRT1.
Results
Our current results indicated that cognitive function in SNI mice was impaired, SIRT1 expression in glutaminergic neurons in the hippocampal CA1 area was downregulated, and synaptic plasticity was altered. Selective knockdown of SIRT1 in hippocampus damaged synaptic plasticity and cognitive function of healthy mice. In addition, the impaired synaptic plasticity and cognitive dysfunction of SNI mice could be improved by the upregulation of SIRT1 expression or enzyme activity.
Conclusions
Reduced SIRT1 expression in hippocampus of SNI mice may induce cognitive impairment associated with chronic pain by mediating the impaired synaptic plasticity.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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