强迫运动和安非他酮对慢性甲基苯丙胺诱导的大鼠认知障碍的神经保护作用：通过调节环磷腺苷反应元件结合蛋白/脑源性神经营养因子信号通路、氧化应激和炎症生物标志物
Neuroprotective Effects of Forced Exercise and Bupropion on Chronic Methamphetamine-induced Cognitive Impairment via Modulation of cAMP Response Element-binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway, Oxidative Stress, and Inflammatory Biomarkers in Rats.
作者信息
Taheri Parastoo, Keshavarzi Saghar, Ebadi Mina, Motaghinejad Majid, Motevalian Manijeh
机构信息
Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
出版信息
Adv Biomed Res. 2018 Dec 19;7:151. doi: 10.4103/abr.abr_11_18. eCollection 2018.
BACKGROUND
Forced exercise can act as non-pharmacologic neuroprotective agent. In current study, we tried the involved molecular mechanisms of protective effects of forced exercise against methamphetamine induced neurodegeneration.
MATERIALS AND METHODS
Forty adult male rats were divided to Group 1 and 2 which received normal saline and methamphetamine (10 mg/kg) respectively for 30 days. Groups 3, 4 and 5 were treated with methamphetamine for first 15 days and then were treated by forced exercise, bupropion (20 mg/kg/day) or combination of them for the following 15 days. Between 26 and 30 days, Morris Water Maze (MWM) was used to evaluate the cognition. On day 31, hippocampus was isolated from each rat and oxidative, antioxidant and inflammatory factors also the level of total and phosphorylated forms of cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) proteins were also evaluated.
RESULTS
Chronic abuse of methamphetamine could decreases cognition and increase malondialdehyde (MDA), Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), while caused decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities all these changes was significant ( < 0.001) in compared to control group while treatment with bupropion, forced exercise and bupropion in combination with forced exercise could prevent all these malicious effects of methamphetamine ( < 0.001). Bupropion, forced exercise and bupropion in combination with forced exercise could activate CREB (both forms) and activates BDNF proteins' expression with < 0.001 in methamphetamine treated rats.
CONCLUSIONS
P-CREB/BDNF signaling pathways might have critical role in forced exercise protective effects against methamphetamine induced neurodegeneration.
背景
强迫运动可作为一种非药物性神经保护剂。在本研究中，我们探究了强迫运动对甲基苯丙胺诱导的神经退行性变的保护作用所涉及的分子机制。
材料与方法
将40只成年雄性大鼠分为1组和2组，分别给予生理盐水和甲基苯丙胺（10 mg/kg），持续30天。第3组、第4组和第5组先接受15天的甲基苯丙胺治疗，随后15天分别接受强迫运动、安非他酮（20 mg/kg/天）或两者联合治疗。在第26天至第30天期间，使用莫里斯水迷宫（MWM）评估认知能力。在第31天，从每只大鼠中分离出海马体，评估氧化、抗氧化和炎症因子，以及环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）蛋白的总形式和磷酸化形式的水平。
结果
长期滥用甲基苯丙胺会降低认知能力，增加丙二醛（MDA）、肿瘤坏死因子α（TNF-α）和白细胞介素-1β（IL-1β）水平，同时导致超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）活性降低。与对照组相比，所有这些变化均具有显著性（P < 0.001）。而使用安非他酮、强迫运动以及安非他酮与强迫运动联合治疗可预防甲基苯丙胺的所有这些有害影响（P < 0.001）。在接受甲基苯丙胺治疗的大鼠中，安非他酮、强迫运动以及安非他酮与强迫运动联合治疗可激活CREB（两种形式）并激活BDNF蛋白的表达，P < 0.001。
结论
P-CREB/BDNF信号通路可能在强迫运动对甲基苯丙胺诱导的神经退行性变的保护作用中起关键作用。
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