Mozaffari Shiva, Ramezany Yasuj Sanaz, Motaghinejad Majid, Motevalian Manijeh, Kheiri Reyhaneh
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Addiction and Risky Behaviors (ReCARB), Psychiatric Center, Iran University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2019 Spring;18(2):745-758. doi: 10.22037/ijpr.2019.2393.
Methamphetamine (METH) abuse causes neurodegeneration. Medicinal herb such as has neuroprotective properties. The current study evaluates the role of CREB-BDNF signaling pathway in mediating the neuroprotective effects of against METH-induced neurodegeneration in rats. Sixty adult male rats were divided randomly into group 1 and group 2 which received 0.7 mL/rat of normal saline and 10 mg/kg of METH intraperitoneally (i.p) respectively, and groups 3, 4, 5 and 6 which treated concurrently with METH (10 mg/kg) and (10, 20, 40 and 80 mg/kg I.P respectively) for 21 days. Morris water maze (MWM) was used to evaluate cognitive activity. According to the critical role of hippocampus in cognitive behavior, the molecular and biochemical parts of our study were done in hippocampus and according to this, hippocampal neurodegenerative parameters and also CREB and BDNF levels were evaluated in isolated hippocampus. METH disturbed the learning, memory, and simultaneous treatment with various doses of reduced the METH-induced cognition disturbances. In addition, METH treatment increased lipid peroxidation and the levels of oxidized form of glutathione (GSSG), interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and Bax, while reducing reduced form of glutathione (GSH), Bcl-2, P-CREB, and BDNF levels in the hippocampus. METH also reduced the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) in the hippocampus. In contrast, (40 and 80 mg/kg) attenuated METH-induced apoptosis, oxidative stress, and inflammation, while elevating P-CREB and BDNF levels. Thus, confers neuroprotection against METH-induced neurodegeneration in hippocampus and this is probably through activation of P-CREB/BDNF signaling pathway.
甲基苯丙胺（METH）滥用会导致神经退行性变。诸如[某种草药名称未给出]之类的药用植物具有神经保护特性。当前研究评估了CREB - BDNF信号通路在介导[某种草药名称未给出]对大鼠METH诱导的神经退行性变的神经保护作用中的作用。60只成年雄性大鼠被随机分为1组和2组，分别腹腔注射（i.p）0.7 mL/只的生理盐水和10 mg/kg的METH，以及3组、4组、5组和6组，这些组同时用METH（10 mg/kg）和[某种草药名称未给出]（分别为10、20、40和80 mg/kg腹腔注射）处理21天。使用莫里斯水迷宫（MWM）评估认知活动。鉴于海马体在认知行为中的关键作用，我们研究的分子和生化部分在海马体中进行，据此，在分离的海马体中评估海马体神经退行性变参数以及CREB和BDNF水平。METH扰乱了学习、记忆，而同时用不同剂量的[某种草药名称未给出]治疗可减轻METH诱导的认知障碍。此外，METH处理增加了脂质过氧化以及氧化型谷胱甘肽（GSSG）、白细胞介素1β（IL - 1β）、肿瘤坏死因子α（TNF - α）和Bax的水平，同时降低了海马体中还原型谷胱甘肽（GSH）、Bcl - 2、磷酸化CREB（P - CREB）和BDNF的水平。METH还降低了海马体中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）的活性。相反，[某种草药名称未给出]（40和80 mg/kg）减轻了METH诱导的细胞凋亡、氧化应激和炎症，同时提高了P - CREB和BDNF水平。因此，[某种草药名称未给出]对海马体中METH诱导的神经退行性变具有神经保护作用，这可能是通过激活P - CREB/BDNF信号通路实现的。
