{"title":"通过减少吗啡暴露大鼠海马的炎症和氧化应激,跑步机运动对认知障碍的年龄依赖性影响:SIRTs 3和4和BDNF的作用。","authors":"Saeedeh Ahmadi Nejad, Mohammad Amin Rajizadeh, Saeedeh Shojaeepour, Shahrzad Azizi, Omid Moradnejad, Tania Dehesh, Faezeh Akhgarandouz, Mansoureh Sabzalizadeh, Atena Alifarsangi","doi":"10.1007/s10522-025-10255-6","DOIUrl":null,"url":null,"abstract":"<p><p>Morphine addiction has many side effects, such as cognitive disorders. On the other hand, old age alone is one of the risk factors for cognitive decline and can increase the risk of addiction. On the other hand, the positive effects of exercise as a non-pharmacological intervention on cognitive disorders have been shown through the increase of growth factors and synaptic proteins. This study will investigate the impacts of exercise on the consequences of morphine addiction in aged rats, relying on the role of oxidative and inflammatory factors as well as SIRT 3, SIRT 4, and BDNF. 56 male Wistar rats were allotted in 8 groups, 4 for young and 4 for old rats.The groups include 1. Control; 2. Exercise; 3. Morphine exposed; 4. Morphine exposed + Exercise.The rats in morphine-exposed groups received morphine for 21 days, and the rats performed treadmill exercises for 4 weeks. The behavioral tests included Morris water maze (MWM), Open field test (OFT), Elevated plus maze (EPM), and Novel object recognition test (NOR), which were done to evaluate cognitive function. The gene expression of TNF, IL-6, BDNF, SIRT 3, and SIRT 4 was measured in the hippocampus tissue by RT-PCR. Also, the levels of MDA, TAC, SOD and GPX were assessed using by related kits. Our results showed that morphine exposure in both young and old rats resulted in cognitive impairments and increased anxiety-like behaviors. Also, morphine exposure reduced BDNF, SIRT1, and SIRT4 and increased TNF and IL-6 gene expression in the hippocampus of rats. However, exercise could improve cognitive impairments and anxiety in both young and old rats and reduce TNF, IL-6, and MDA and elevation of BDNF, SIRT 3, and SIRT 4 gene expression and TAC, SOD, and GPX levels in the hippocampus tissue. Exercise could improve cognitive impairments following morphine exposure in young and old rats by reducing inflammation and oxidative stress and increasing expression of BDNF, SIRT 3, and SIRT 4.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"113"},"PeriodicalIF":4.1000,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The age-dependent impacts of treadmill exercise on cognitive impairments by reducing inflammation and oxidative stress in the hippocampus of morphine-exposed rats: the role of SIRTs 3 &4 and BDNF.\",\"authors\":\"Saeedeh Ahmadi Nejad, Mohammad Amin Rajizadeh, Saeedeh Shojaeepour, Shahrzad Azizi, Omid Moradnejad, Tania Dehesh, Faezeh Akhgarandouz, Mansoureh Sabzalizadeh, Atena Alifarsangi\",\"doi\":\"10.1007/s10522-025-10255-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Morphine addiction has many side effects, such as cognitive disorders. On the other hand, old age alone is one of the risk factors for cognitive decline and can increase the risk of addiction. On the other hand, the positive effects of exercise as a non-pharmacological intervention on cognitive disorders have been shown through the increase of growth factors and synaptic proteins. This study will investigate the impacts of exercise on the consequences of morphine addiction in aged rats, relying on the role of oxidative and inflammatory factors as well as SIRT 3, SIRT 4, and BDNF. 56 male Wistar rats were allotted in 8 groups, 4 for young and 4 for old rats.The groups include 1. Control; 2. Exercise; 3. Morphine exposed; 4. Morphine exposed + Exercise.The rats in morphine-exposed groups received morphine for 21 days, and the rats performed treadmill exercises for 4 weeks. The behavioral tests included Morris water maze (MWM), Open field test (OFT), Elevated plus maze (EPM), and Novel object recognition test (NOR), which were done to evaluate cognitive function. The gene expression of TNF, IL-6, BDNF, SIRT 3, and SIRT 4 was measured in the hippocampus tissue by RT-PCR. Also, the levels of MDA, TAC, SOD and GPX were assessed using by related kits. Our results showed that morphine exposure in both young and old rats resulted in cognitive impairments and increased anxiety-like behaviors. Also, morphine exposure reduced BDNF, SIRT1, and SIRT4 and increased TNF and IL-6 gene expression in the hippocampus of rats. However, exercise could improve cognitive impairments and anxiety in both young and old rats and reduce TNF, IL-6, and MDA and elevation of BDNF, SIRT 3, and SIRT 4 gene expression and TAC, SOD, and GPX levels in the hippocampus tissue. Exercise could improve cognitive impairments following morphine exposure in young and old rats by reducing inflammation and oxidative stress and increasing expression of BDNF, SIRT 3, and SIRT 4.</p>\",\"PeriodicalId\":8909,\"journal\":{\"name\":\"Biogerontology\",\"volume\":\"26 3\",\"pages\":\"113\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-05-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biogerontology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10522-025-10255-6\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biogerontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10522-025-10255-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
吗啡成瘾有很多副作用,比如认知障碍。另一方面,年老本身就是认知能力下降的风险因素之一,并可能增加成瘾的风险。另一方面,运动作为一种非药物干预对认知障碍的积极作用已通过生长因子和突触蛋白的增加而得到证实。本研究将通过氧化和炎症因子以及SIRT 3、SIRT 4和BDNF的作用,探讨运动对老年大鼠吗啡成瘾后果的影响。雄性Wistar大鼠56只,分为8组,年轻组4只,老年组4只。分组包括:1;控制;2. 锻炼;3. 吗啡暴露;4. 吗啡暴露+运动。吗啡暴露组大鼠连续注射吗啡21天,进行跑步机运动4周。行为学测试包括Morris水迷宫(MWM)、Open field test (OFT)、Elevated plus maze (EPM)和Novel object recognition test (NOR)。采用RT-PCR法检测海马组织中TNF、IL-6、BDNF、SIRT 3、SIRT 4的基因表达。采用相关试剂盒检测各组大鼠血清MDA、TAC、SOD、GPX水平。我们的研究结果表明,吗啡暴露在年轻和年老的大鼠中都会导致认知障碍和增加焦虑样行为。吗啡暴露降低大鼠海马BDNF、SIRT1和SIRT4,增加TNF和IL-6基因表达。然而,运动可以改善年轻和老年大鼠的认知障碍和焦虑,降低TNF、IL-6和MDA,升高BDNF、SIRT 3和SIRT 4基因表达以及海马组织中TAC、SOD和GPX水平。运动可以通过减少炎症和氧化应激以及增加BDNF、SIRT 3和SIRT 4的表达来改善吗啡暴露后的认知障碍。
The age-dependent impacts of treadmill exercise on cognitive impairments by reducing inflammation and oxidative stress in the hippocampus of morphine-exposed rats: the role of SIRTs 3 &4 and BDNF.
Morphine addiction has many side effects, such as cognitive disorders. On the other hand, old age alone is one of the risk factors for cognitive decline and can increase the risk of addiction. On the other hand, the positive effects of exercise as a non-pharmacological intervention on cognitive disorders have been shown through the increase of growth factors and synaptic proteins. This study will investigate the impacts of exercise on the consequences of morphine addiction in aged rats, relying on the role of oxidative and inflammatory factors as well as SIRT 3, SIRT 4, and BDNF. 56 male Wistar rats were allotted in 8 groups, 4 for young and 4 for old rats.The groups include 1. Control; 2. Exercise; 3. Morphine exposed; 4. Morphine exposed + Exercise.The rats in morphine-exposed groups received morphine for 21 days, and the rats performed treadmill exercises for 4 weeks. The behavioral tests included Morris water maze (MWM), Open field test (OFT), Elevated plus maze (EPM), and Novel object recognition test (NOR), which were done to evaluate cognitive function. The gene expression of TNF, IL-6, BDNF, SIRT 3, and SIRT 4 was measured in the hippocampus tissue by RT-PCR. Also, the levels of MDA, TAC, SOD and GPX were assessed using by related kits. Our results showed that morphine exposure in both young and old rats resulted in cognitive impairments and increased anxiety-like behaviors. Also, morphine exposure reduced BDNF, SIRT1, and SIRT4 and increased TNF and IL-6 gene expression in the hippocampus of rats. However, exercise could improve cognitive impairments and anxiety in both young and old rats and reduce TNF, IL-6, and MDA and elevation of BDNF, SIRT 3, and SIRT 4 gene expression and TAC, SOD, and GPX levels in the hippocampus tissue. Exercise could improve cognitive impairments following morphine exposure in young and old rats by reducing inflammation and oxidative stress and increasing expression of BDNF, SIRT 3, and SIRT 4.
期刊介绍:
The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments.
Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.