{"title":"Inhibition of Extracellular Signal-Regulated Kinase Activity Improves Cognitive Function in Mice Subjected to Myocardial Infarction.","authors":"Yibo Yin, Xin Li, Xiaoxua Zhang, Xinru Yuan, Xingji You, Jingxiang Wu","doi":"10.1007/s12012-024-09877-y","DOIUrl":null,"url":null,"abstract":"<p><p>Cognitive impairment is a commonly observed complication following myocardial infarction; however, the underlying mechanisms are still not well understood. The most recent research suggests that extracellular signal-regulated kinase (ERK) plays a critical role in the development and occurrence of cognitive dysfunction-related diseases. This study aims to explore whether the ERK inhibitor U0126 targets the ERK/Signal Transducer and Activator of Transcription 1 (STAT1) pathway to ameliorate cognitive impairment after myocardial infarction. To establish a mouse model of myocardial infarction, we utilized various techniques including Echocardiography, Hematoxylin-eosin (HE) staining, Elisa, Open field test, Elevated plus maze test, and Western blot analysis to assess mouse cardiac function, cognitive function, and signal transduction pathways. For further investigation into the mechanisms of cognitive function and signal transduction, we administered the ERK inhibitor U0126 via intraperitoneal injection. Reduced total distance and activity range were observed in mice subjected to myocardial infarction during the open field test, along with decreased exploration of the open arms in the elevated plus maze test. However, U0126 treatment exhibited a significant improvement in cognitive decline, indicating a protective effect through the inhibition of the ERK/STAT1 signaling pathway. Hence, this study highlights the involvement of the ERK/STAT1 pathway in regulating cognitive dysfunction following myocardial infarction and establishes U0126 as a promising therapeutic target.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12012-024-09877-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/8 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Cognitive impairment is a commonly observed complication following myocardial infarction; however, the underlying mechanisms are still not well understood. The most recent research suggests that extracellular signal-regulated kinase (ERK) plays a critical role in the development and occurrence of cognitive dysfunction-related diseases. This study aims to explore whether the ERK inhibitor U0126 targets the ERK/Signal Transducer and Activator of Transcription 1 (STAT1) pathway to ameliorate cognitive impairment after myocardial infarction. To establish a mouse model of myocardial infarction, we utilized various techniques including Echocardiography, Hematoxylin-eosin (HE) staining, Elisa, Open field test, Elevated plus maze test, and Western blot analysis to assess mouse cardiac function, cognitive function, and signal transduction pathways. For further investigation into the mechanisms of cognitive function and signal transduction, we administered the ERK inhibitor U0126 via intraperitoneal injection. Reduced total distance and activity range were observed in mice subjected to myocardial infarction during the open field test, along with decreased exploration of the open arms in the elevated plus maze test. However, U0126 treatment exhibited a significant improvement in cognitive decline, indicating a protective effect through the inhibition of the ERK/STAT1 signaling pathway. Hence, this study highlights the involvement of the ERK/STAT1 pathway in regulating cognitive dysfunction following myocardial infarction and establishes U0126 as a promising therapeutic target.
认知功能障碍是心肌梗死后常见的并发症,但其潜在机制仍不十分清楚。最新研究表明,细胞外信号调节激酶(ERK)在认知功能障碍相关疾病的发生和发展中起着关键作用。本研究旨在探讨ERK抑制剂U0126是否能靶向ERK/信号转导和转录激活因子1(STAT1)通路,以改善心肌梗死后的认知障碍。为了建立心肌梗死小鼠模型,我们采用了各种技术,包括超声心动图、血栓素-伊红(HE)染色、Elisa、开阔地试验、高架迷宫试验和 Western 印迹分析,以评估小鼠的心脏功能、认知功能和信号转导通路。为了进一步研究认知功能和信号转导的机制,我们通过腹腔注射ERK抑制剂U0126。我们观察到,心肌梗死小鼠在开阔地测试中的总距离和活动范围都有所减少,同时在高架加迷宫测试中对开阔臂的探索也有所减少。然而,U0126治疗可显著改善认知能力的下降,这表明它通过抑制ERK/STAT1信号通路起到了保护作用。因此,这项研究强调了ERK/STAT1通路参与调节心肌梗死后的认知功能障碍,并将U0126确立为一个有前景的治疗靶点。
期刊介绍:
Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.