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Selenothymidine protects against biochemical and behavioral alterations induced by ICV-STZ model of dementia in mice
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-08-16 , DOI: 10.1016/j.cbi.2018.08.004
Gustavo Roberto Thomé , Vitor Antunes Oliveira , Maria Rosa Chitolina Schetinger , Rogério Aquino Saraiva , Diego Souza , Oscar Endrigo Dorneles Rodrigues , João Batista Teixeira Rocha , Rafael Porto Ineu , Maria Ester Pereira

The present study evaluated the neuroprotective effects of one selenium-containing AZT derivative compound (S1073) in memory and learning impairment caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice causes impairment of energy metabolism with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein oxidation (DCFH), TBARS and thiol content were measured. Swiss adult mice were pre-treated with S1073 [1 mmol/kg] (i.p.) and after 30 min of the injection received a bilateral dose of STZ [11.3 μmol/l]. After 8 days' STZ injection, we performed the behavioral experiments (Beaker test, Open field and Morris water maze task). ICV-STZ caused significant learning and memory impairments, which were significantly improved by S1073 pre-treatment. A significant increase in cerebral DFCH, TBARS levels and AChE activity and a disturbance in the memory and learning were observed in ICV-STZ injected animals. S1073 significantly ameliorated all alterations induced by ICV-STZ in mice. All these findings support the neuroprotective role of S1073 in mice model of Alzheimer's dementia-type induced by ICV-STZ, which may be associated with its antioxidant activity and/or with its inhibitory effect in brain AChE. In fact, in silico analysis indicated that S1073 may be an inhibitor of AChE.



中文翻译:

硒代胸苷可预防ICV-STZ痴呆模型在小鼠体内引起的生化和行为改变

本研究评估了一种含硒的AZT衍生物化合物(S1073)在对脑室内室链脲佐菌素(ICV-STZ)引起的记忆和学习障碍中的神经保护作用。小鼠中的ICV-STZ导致能量代谢受损,并伴有氧化损伤和胆碱能功能障碍,并为阿尔茨海默氏病(AD)偶发性痴呆症提供了相关模型。测量了乙酰胆碱酯酶(AChE),过氧化氢酶(CAT),二氯荧光素氧化(DCFH),TBARS和硫醇含量。瑞士成年小鼠用S1073 [1 mmol / kg](ip)进行了预处理,注射30分钟后接受了STZ的双边剂量[11.3μmol/ l]。注射STZ 8天后,我们进行了行为实验(烧杯测试,开阔野外和莫里斯水迷宫任务)。ICV-STZ导致严重的学习和记忆障碍,通过S1073预处理可以显着改善。在注射ICV-STZ的动物中观察到脑DFCH,TBARS水平和AChE活性显着增加,并且记忆和学习受到干扰。S1073显着改善了ICV-STZ诱导的小鼠所有改变。所有这些发现支持S1073在ICV-STZ诱导的阿尔茨海默氏痴呆型小鼠模型中的神经保护作用,这可能与其抗氧化活性和/或其对脑AChE的抑制作用有关。实际上,所有这些发现支持S1073在ICV-STZ诱导的阿尔茨海默氏痴呆型小鼠模型中的神经保护作用,这可能与其抗氧化活性和/或其对脑AChE的抑制作用有关。实际上,所有这些发现都支持S1073在ICV-STZ诱导的阿尔茨海默氏痴呆型小鼠模型中的神经保护作用,这可能与其抗氧化活性和/或其对脑AChE的抑制作用有关。实际上,计算机分析的结果表明S1073可能是AChE的抑制剂。

更新日期:2018-08-16
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