Intracerebroventricular Injection of MHY1485 Blocked the Beneficial Effect of Adiponectin on Aversive Memory in the STZ Model of Dementia.

Samira Rashtiani, Iran Goudarzi, Adele Jafari, Kambiz Rohampour
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Abstract

Background: The most prominent adipokine, adiponectin (APN), has an adverse relationship with the malfunction of adipose tissue. Obesity causes a decrease in plasma APN levels, which eventually results in insulin resistance and diabetes. In this study, we assessed how the effects of APN on memory are influenced by the insulin receptor substrate-1 (IRS-1) and the mammalian target of rapamycin (mTOR) pathways.

Methods: Streptozotocin (STZ) 3 mg/kg intracerebroventricular injections on days 1 and 3 following cannulation were used to create an animal model of Alzheimer's disease. The acquisition phase was preceded by injections of MHY and adiponectin. For the passive avoidance task, the stepthrough latency and total duration in the dark compartment were recorded and evaluated, and the preference index was calculated for the novel object identification test. IRS-1 protein expression in the hippocampus was assessed by western blotting.

Results: STZ reduced the step-through latency (STL), which rose significantly (P≤0.001) in the APN+STZ group. The memory-improving effects of APN were reversed when MHY was administered first (P≤0.001). The STZ and APN+STZ+MHY groups both had a substantial decline in the preference index (P≤0.01). Compared to the control group, the STZ group's expression of the IRS- 1 protein was dramatically reduced (P≤0.0001). In contrast to the APN+STZ group, the MHYtreated group likewise showed decreased IRS-1 protein expression (P≤0.0001), but APN+STZ was able to enhance IRS-1 expression rate (P≤0.0001).

Conclusion: In a rat model of AD, we found that adiponectin improved aversive and cognitive memory, which is at least partially mediated by the mTOR signaling cascade.

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脑室注射MHY1485阻断脂联素对STZ痴呆模型厌恶记忆的有益作用。
背景:最重要的脂肪因子脂联素(APN)与脂肪组织功能障碍有不利关系。肥胖导致血浆APN水平下降,最终导致胰岛素抵抗和糖尿病。在这项研究中,我们评估了APN对记忆的影响如何受到胰岛素受体底物-1 (IRS-1)和哺乳动物雷帕霉素靶点(mTOR)途径的影响。方法:采用链脲佐菌素(STZ) 3 mg/kg脑室注射,分别于插管后第1天和第3天建立阿尔茨海默病动物模型。在获取阶段之前注射MHY和脂联素。对于被动回避任务,记录并评估在黑暗隔间的步进潜伏期和总持续时间,并计算新物体识别测试的偏好指数。western blotting检测海马组织中IRS-1蛋白的表达。结果:STZ降低了跨步潜伏期(STL), APN+STZ组显著升高(P≤0.001)。当首次给予MHY时,APN的记忆改善作用逆转(P≤0.001)。STZ组和APN+STZ+MHY组的偏好指数均显著下降(P≤0.01)。与对照组相比,STZ组IRS- 1蛋白表达量显著降低(P≤0.0001)。与APN+STZ组相比,mhy处理组也显示IRS-1蛋白表达降低(P≤0.0001),但APN+STZ能够提高IRS-1表达率(P≤0.0001)。结论:在AD大鼠模型中,我们发现脂联素改善了厌恶记忆和认知记忆,这至少部分是由mTOR信号级联介导的。
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来源期刊
Central nervous system agents in medicinal chemistry
Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology
CiteScore
2.10
自引率
0.00%
发文量
21
期刊介绍: Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.
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