{"title":"探索术前睡眠不足对小鼠认知功能的影响:微胶质细胞活化和铁代谢的作用","authors":"Yong Chen, Peng Yao, Yujuan You, Xianliang Xing, Xifeng Wang, Weijian Zhou, Yanhui Hu, Enjun Lei","doi":"10.1155/2024/4376698","DOIUrl":null,"url":null,"abstract":"<p><i>Background</i>. Perioperative neurocognitive disorders (PND) are a significant concern, particularly for aged individuals. Sleep fragmentation (SF), a common condition in older adults, is considered a risk factor for PND. The present study explored the impact of SF on cognitive function and its association with microglial activation and iron metabolism. <i>Methods</i>. Adult and aged C57BL/6J mice were subjected to tibial fracture surgery (TFS) and varying durations of SF. Cognitive function was assessed using the Morris water maze and fear conditioning experiments. Microglial activation was evaluated by measuring CD68 protein expression and inflammatory cytokine levels. Iron metabolism and ferroptosis-related proteins were also examined. <i>Results</i>. SF significantly impacted spatial memory and conditioned fear responses in mice, with aged mice showing greater susceptibility. Microglial activation, indicated by changes in CD68 protein expression and inflammatory cytokine levels, was observed in mice exposed to SF. Alterations in iron metabolism, as evidenced by changes in hippocampal iron content and expression of ferroptosis-related proteins, were also observed in these mice. <i>Conclusion</i>. SF can lead to significant cognitive impairment, particularly in aged mice, likely mediated through microglial activation and dysregulated iron metabolism. These findings provide novel insights into the pathogenesis of PND and suggest potential targets for intervention. <i>Significance</i>. This study illuminates the complex interactions between SF, microglial activation, and cognitive function. It highlights the importance of sleep quality for cognitive health in older adults and points to potential therapeutic strategies for preventing PND, including targeting microglial activation and iron metabolism.</p>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the Impact of Preoperative Sleep Fragmentation on Cognitive Function in Mice: The Role of Microglial Activation and Iron Metabolism\",\"authors\":\"Yong Chen, Peng Yao, Yujuan You, Xianliang Xing, Xifeng Wang, Weijian Zhou, Yanhui Hu, Enjun Lei\",\"doi\":\"10.1155/2024/4376698\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><i>Background</i>. Perioperative neurocognitive disorders (PND) are a significant concern, particularly for aged individuals. Sleep fragmentation (SF), a common condition in older adults, is considered a risk factor for PND. The present study explored the impact of SF on cognitive function and its association with microglial activation and iron metabolism. <i>Methods</i>. Adult and aged C57BL/6J mice were subjected to tibial fracture surgery (TFS) and varying durations of SF. Cognitive function was assessed using the Morris water maze and fear conditioning experiments. Microglial activation was evaluated by measuring CD68 protein expression and inflammatory cytokine levels. Iron metabolism and ferroptosis-related proteins were also examined. <i>Results</i>. SF significantly impacted spatial memory and conditioned fear responses in mice, with aged mice showing greater susceptibility. Microglial activation, indicated by changes in CD68 protein expression and inflammatory cytokine levels, was observed in mice exposed to SF. Alterations in iron metabolism, as evidenced by changes in hippocampal iron content and expression of ferroptosis-related proteins, were also observed in these mice. <i>Conclusion</i>. SF can lead to significant cognitive impairment, particularly in aged mice, likely mediated through microglial activation and dysregulated iron metabolism. These findings provide novel insights into the pathogenesis of PND and suggest potential targets for intervention. <i>Significance</i>. This study illuminates the complex interactions between SF, microglial activation, and cognitive function. It highlights the importance of sleep quality for cognitive health in older adults and points to potential therapeutic strategies for preventing PND, including targeting microglial activation and iron metabolism.</p>\",\"PeriodicalId\":15381,\"journal\":{\"name\":\"Journal of Clinical Pharmacy and Therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-05-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Pharmacy and Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1155/2024/4376698\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Pharmacy and Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/4376698","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
背景。围手术期神经认知障碍(PND)是一个值得关注的重要问题,尤其是对老年人而言。睡眠片段化(SF)是老年人的常见病,被认为是导致围手术期神经认知障碍的一个危险因素。本研究探讨了 SF 对认知功能的影响及其与小胶质细胞活化和铁代谢的关系。研究方法成年和老龄 C57BL/6J 小鼠接受胫骨骨折手术(TFS)和不同持续时间的 SF。使用莫里斯水迷宫和恐惧条件反射实验评估认知功能。通过测量 CD68 蛋白表达和炎性细胞因子水平评估了小胶质细胞的活化情况。此外还检测了铁代谢和铁蛋白相关蛋白。结果SF 明显影响小鼠的空间记忆和条件性恐惧反应,老年小鼠更易受影响。在暴露于 SF 的小鼠中,CD68 蛋白表达和炎性细胞因子水平的变化表明小胶质细胞活化。在这些小鼠中还观察到铁代谢的改变,表现为海马铁含量和铁变态反应相关蛋白表达的变化。结论SF 可导致严重的认知障碍,尤其是在老年小鼠中,这可能是通过小胶质细胞激活和铁代谢失调介导的。这些发现为 PND 的发病机制提供了新的见解,并提出了潜在的干预目标。意义重大。这项研究揭示了SF、小胶质细胞活化和认知功能之间复杂的相互作用。它强调了睡眠质量对老年人认知健康的重要性,并指出了预防 PND 的潜在治疗策略,包括针对小胶质细胞活化和铁代谢的治疗策略。
Exploring the Impact of Preoperative Sleep Fragmentation on Cognitive Function in Mice: The Role of Microglial Activation and Iron Metabolism
Background. Perioperative neurocognitive disorders (PND) are a significant concern, particularly for aged individuals. Sleep fragmentation (SF), a common condition in older adults, is considered a risk factor for PND. The present study explored the impact of SF on cognitive function and its association with microglial activation and iron metabolism. Methods. Adult and aged C57BL/6J mice were subjected to tibial fracture surgery (TFS) and varying durations of SF. Cognitive function was assessed using the Morris water maze and fear conditioning experiments. Microglial activation was evaluated by measuring CD68 protein expression and inflammatory cytokine levels. Iron metabolism and ferroptosis-related proteins were also examined. Results. SF significantly impacted spatial memory and conditioned fear responses in mice, with aged mice showing greater susceptibility. Microglial activation, indicated by changes in CD68 protein expression and inflammatory cytokine levels, was observed in mice exposed to SF. Alterations in iron metabolism, as evidenced by changes in hippocampal iron content and expression of ferroptosis-related proteins, were also observed in these mice. Conclusion. SF can lead to significant cognitive impairment, particularly in aged mice, likely mediated through microglial activation and dysregulated iron metabolism. These findings provide novel insights into the pathogenesis of PND and suggest potential targets for intervention. Significance. This study illuminates the complex interactions between SF, microglial activation, and cognitive function. It highlights the importance of sleep quality for cognitive health in older adults and points to potential therapeutic strategies for preventing PND, including targeting microglial activation and iron metabolism.
期刊介绍:
The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including:
Rational therapeutics
Evidence-based practice
Safety, cost-effectiveness and clinical efficacy of drugs
Drug interactions
Clinical impact of drug formulations
Pharmacogenetics
Personalised, stratified and translational medicine
Clinical pharmacokinetics.