Animal model for sporadic dementia of Alzheimer’s type (SDAT) using streptozotocin and lipopolysaccharide combinations in rats

Rahadian Yudo Hartantyo, Mohammad Rizky Mochtar Hidayat, A. Azzam, M. Mulyati
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Abstract

Sporadic dementia of Alzheimer’s type (SDAT) pathogenesis has not been revealed completely due to the difficulty in creating an appropriate animal model. The purpose of this study was to investigate the effect of single-dose intraperitoneal (IP) induction of streptozotocin (STZ) and lipopolysaccharide (LPS) on the β-amyloid levels and the brain function of experimental rats. Eighteen rats were divided into three groups i.e. control, TRE1 (STZ 60 mg.kg-1 BW + LPS 3 mg.kg-1 BW), and TRE2 (STZ 30 mg.kg-1 BW + LPS 1.5 mg.kg-1 BW). The substances were administered in a single dose. Behavioral tests were started at day-30 after injection, we performed Morris water maze (MWM) and novel object recognition (NOR) tests. Afterward, we measured whole brain and serum β-amyloid levels, as one of the biomarkers of Alzheimer’s Disease (AD), using the ELISA method. In MWM tests, the escape latency and time spent in the target quadrant of treatment groups were significantly higher than those in control at the day-5 MWM test and probe trial. The rats in treatment groups have negative discrimination indexes in NOR tasks, indicating that the rats could not remember the familiar object. Intraperitoneal STZ and LPS significantly increase soluble brain β-amyloid levels of treatment groups than those in the control group. In conclusion, the treatment of STZ (60 mg.kg-1 BW) and LPS (3 mg.kg-1 BW) indicated spatial and recognition memory impairment, along with an increase of brain soluble β-amyloid level in rats.
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链脲佐菌素和脂多糖联合应用建立大鼠散发性阿尔茨海默氏型痴呆(SDAT)动物模型
散发性阿尔茨海默氏型痴呆(SDAT)的发病机制由于难以建立合适的动物模型而尚未完全揭示。本研究旨在探讨单剂量腹腔注射链脲佐菌素(STZ)和脂多糖(LPS)对实验大鼠β-淀粉样蛋白水平和脑功能的影响。18只大鼠分为对照组、TRE1 (STZ 60 mg)组。kg- 1bw + LPS 3mg。kg-1 BW), TRE2 (STZ 30 mg。kg- 1bw + LPS 1.5 mg。公斤BW)。这些物质是一次性给药的。行为学测试于注射后第30天开始,我们进行Morris水迷宫(MWM)和新物体识别(NOR)测试。随后,我们使用ELISA方法测量了全脑和血清β-淀粉样蛋白水平,β-淀粉样蛋白是阿尔茨海默病(AD)的生物标志物之一。在MWM试验中,在第5天MWM试验和探针试验中,治疗组的逃避潜伏期和在目标象限停留的时间均显著高于对照组。实验组大鼠在NOR任务中的辨别指数为负,表明大鼠不能记住熟悉的物体。与对照组相比,腹腔注射STZ和LPS显著提高了各治疗组脑可溶性β-淀粉样蛋白水平。综上所述,STZ (60 mg。kg-1 BW)和LPS (3 mg。kg- 1bw)提示大鼠空间记忆和识别记忆障碍,并伴有脑可溶性β-淀粉样蛋白水平升高。
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