跑步机运动通过减轻吗啡暴露大鼠海马体中的炎症和氧化应激对认知障碍的年龄依赖性影响：SIRTs 3和4以及脑源性神经营养因子的作用

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.

作者信息

Nejad Saeedeh Ahmadi, Rajizadeh Mohammad Amin, Shojaeepour Saeedeh, Azizi Shahrzad, Moradnejad Omid, Dehesh Tania, Akhgarandouz Faezeh, Sabzalizadeh Mansoureh, Alifarsangi Atena

机构信息

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.

出版信息

Biogerontology. 2025 May 26;26(3):113. doi: 10.1007/s10522-025-10255-6.

DOI:10.1007/s10522-025-10255-6

PMID:40418392

Abstract

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.

摘要

吗啡成瘾有许多副作用，如认知障碍。另一方面，仅衰老就是认知能力下降的风险因素之一，并且会增加成瘾风险。另一方面，运动作为一种非药物干预手段，已通过生长因子和突触蛋白的增加，显示出对认知障碍的积极影响。本研究将依靠氧化和炎症因子以及SIRT 3、SIRT 4和脑源性神经营养因子（BDNF）的作用，研究运动对老年大鼠吗啡成瘾后果的影响。56只雄性Wistar大鼠被分为8组，4组为年轻大鼠，4组为老年大鼠。这些组包括：1. 对照组；2. 运动组；3. 吗啡暴露组；4. 吗啡暴露+运动组。吗啡暴露组的大鼠接受吗啡注射21天，大鼠进行4周的跑步机运动。行为测试包括莫里斯水迷宫（MWM）、旷场试验（OFT）、高架十字迷宫（EPM）和新物体识别试验（NOR），用于评估认知功能。通过逆转录聚合酶链反应（RT-PCR）测量海马组织中肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、BDNF、SIRT 3和SIRT 4的基因表达。此外，使用相关试剂盒评估丙二醛（MDA）、总抗氧化能力（TAC）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）的水平。我们的结果表明，年轻和老年大鼠的吗啡暴露均导致认知障碍，并增加类似焦虑的行为。此外，吗啡暴露降低了大鼠海马中BDNF、SIRT1和SIRT4的水平，并增加了TNF和IL-6的基因表达。然而，运动可以改善年轻和老年大鼠的认知障碍和焦虑，并降低TNF、IL-6和MDA水平，提高海马组织中BDNF、SIRT 3和SIRT 4的基因表达以及TAC、SOD和GPX水平。运动可以通过减轻炎症和氧化应激以及增加BDNF、SIRT 3和SIRT 4的表达，改善年轻和老年大鼠吗啡暴露后的认知障碍。