Hippocampal synaptic plasticity injury mediated by SIRT1 downregulation is involved in chronic pain-related cognitive dysfunction

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2023-08-17 DOI:10.1111/cns.14410

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

{"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}

引用次数: 0

Abstract

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 SIRT1^flox/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.

Abstract Image

查看原文本刊更多论文

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

目的与慢性疼痛相关的认知功能障碍可能是由突触可塑性受损引起的。考虑到沉默信息调节因子 1（SIRT1）对突触可塑性的影响，我们探讨了 SIRT1 在慢性疼痛引起的认知功能障碍中的确切作用。方法我们用恐惧条件反射测试（FCT）评估了小鼠在幸免神经损伤（SNI）模型后的记忆能力。用 Western 印迹法和免疫荧光法分析 SIRT1 的表达水平。通过高尔基体染色、透射电子显微镜和长期电位（LTP）检测海马突触可塑性。在干预研究中，向SIRT1flox/flox小鼠注射AAV9-CaMKIIα-Cre-EGFP以敲除SIRT1的表达水平。此外，给 SNI 小鼠注射 AAV2/9-CaMKIIα-SIRT1-3*Flag-GFP 或 SRT1720 以提高 SIRT1 的表达水平或酶活性。结果我们目前的研究结果表明，SNI 小鼠的认知功能受损，海马 CA1 区谷氨酸能神经元中的 SIRT1 表达下调，突触可塑性发生改变。选择性敲除海马中的 SIRT1 会损害健康小鼠的突触可塑性和认知功能。此外，上调 SIRT1 的表达或酶活性可改善 SNI 小鼠受损的突触可塑性和认知功能障碍。结论 SNI 小鼠海马中 SIRT1 表达的降低可能通过介导受损的突触可塑性，诱发与慢性疼痛相关的认知功能障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

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.