Protective Effects of Co-administration of Zinc and Selenium Against Streptozotocin-Induced Alzheimer's Disease: Behavioral, Mitochondrial Oxidative Stress, and GPR39 Expression Alterations in Rats
Protective Effects of Co-administration of Zinc and Selenium Against Streptozotocin-Induced Alzheimer's Disease: Behavioral, Mitochondrial Oxidative Stress, and GPR39 Expression Alterations in Rats
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DOI：
10.1007/s12640-020-00226-9
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发表时间：
2020-06-05
影响因子：
3.7
通讯作者：
Navabi, Seyedeh Parisa
中科院分区：
文献类型：
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作者：
Farbood, Yaghoob;Sarkaki, Alireza;Navabi, Seyedeh Parisa
微量金属如锌（Zn）和硒（Se）浓度的变化可病理性地导致神经退行性疾病如阿尔茨海默病（AD）。已有研究表明线粒体功能障碍在AD的发病机制中起重要作用。雄性Wistar大鼠随机分为5组：假手术组（Sham）、AD组（STZ组）、AD + Zn组（Zn组）、AD + Zn组（STZ组）。AD + Se组腹腔注射Se 0.1mg/kg，AD + Zn + Se组腹腔注射Zn 10 mg/kg + Se 0.1mg/kg。在研究结束时，进行行为测试和线粒体氧化应激和GPR 39基因表达评估。与STZ组相比，锌和硒的共同管理显着降低了线粒体膜的潜在崩溃，活性氧水平和脂质过氧化水平，而显着增加认知能力，超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶和过氧化氢酶活性的脑线粒体。此外，在共处理组中未观察到GPR 39表达的显著变化。目前的研究结果表明，ZnR/GPR 39受体，线粒体功能障碍和氧化应激在AD的发病机制中发挥重要作用。锌和硒的联合治疗改善了STZ诱导的AD引起的认知能力、线粒体功能障碍和氧化应激。因此，改善线粒体功能的治疗方法可以有效预防AD的发生和进展。
Changes in the concentrations of trace metals such as zinc (Zn) and selenium (Se) can pathologically lead to neurodegenerative conditions such as the Alzheimer's disease (AD). Previous studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of AD. Several male Wistar rats were randomly divided into five groups: sham group, AD group that received 3 mg/kg of streptozotocin (STZ) intracerebroventricularly, AD + Zn group that received 10 mg/kg of Zn intraperitoneally (i.p.) for 1 week, AD + Se group that received 0.1 mg/kg of Se i.p. for 1 week, and AD + Zn + Se group that received 10 mg/kg of Zn i.p. plus 0.1 mg/kg of Se i.p. for 1 week. At end of the study, behavioral tests and mitochondrial oxidative stress and GPR39 gene expression evaluations were carried out. Co-administration of Zn and Se significantly decreased the potential collapse of mitochondrial membrane, reactive oxygen species levels, and lipid peroxidation levels while significantly increased cognitive performance, superoxide dismutase (SOD), glutathione peroxidase, and catalase activity in the brain mitochondria compared with the STZ group. In addition, no significant changes were observed in GPR39 expression in the co-treated group. Findings of the current study showed that ZnR/GPR39 receptor, mitochondrial dysfunction, and oxidative stress play important roles in the pathogenesis of AD. Co-treatment of Zn and Se improved the cognitive performance, mitochondrial dysfunction, and oxidative stress caused by STZ-induced AD. Therefore, therapeutic approaches to improve mitochondrial function could be effective in preventing the initiation and progression of AD.