大麻素1型受体拮抗剂在阿尔茨海默病动物模型中损害空间记忆并增加Tau基因表达

Q3 Veterinary
Archives of Razi Institute Pub Date : 2024-10-31 eCollection Date: 2024-10-01 DOI:10.32592/ARI.2024.79.5.935
B Tavakoli-Far, M Zeraati, S Choopani, P Falah, P Darabi, R Mazloom, G Bayat, M Hosseini, M Goudarzvand
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引用次数: 0

摘要

阿尔茨海默病是一种神经退行性疾病,其特征是β-淀粉样蛋白和tau两种不同蛋白质的积累。本研究的目的是研究海马双侧给予大麻素受体拮抗剂(AM251)对阿尔茨海默病模型中空间记忆和tau基因表达的影响。将β-淀粉样蛋白双侧注入Wistar雄性大鼠海马诱导阿尔茨海默病。然后将大鼠分为四组:对照组(以蒸馏水作为β-淀粉样蛋白毒素的溶剂)、病变组(以β-淀粉样蛋白为溶剂)、β-淀粉样蛋白+ DMSO组(作为拮抗剂溶剂)和AM251拮抗剂接受组。在Morris水迷宫试验的训练过程中,大麻素1受体拮抗剂AM251的拮抗剂以5、25和100 ng的剂量连续4天双侧给予海马。为了评估动物的空间记忆,我们分析了以下参数:行进距离、到达隐藏平台的延迟时间、动物的速度和tau基因的实时表达。注射β-淀粉样蛋白和大麻素拮抗剂AM251后,大鼠空间记忆指标明显受损。注射β-淀粉样蛋白后,大鼠tau蛋白mRNA表达增加。然而,大麻素拮抗剂和β-淀粉样蛋白组之间没有显著差异。这些结果表明β-淀粉样蛋白毒素对空间记忆具有破坏作用,大麻素系统在记忆形成和巩固中发挥积极作用,但这些发现还需要进一步的研究来证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Cannabinoid Type 1 Receptor Antagonist Impairs Spatial Memory and Increases the Tau Gene Expression in an Animal Model of the Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disease that is characterized by the accumulation of two different proteins, β-amyloid and tau. The objective of the present study was to examine the impact of bilateral administration of the cannabinoid receptor antagonist (AM251) in the hippocampus on spatial memory and tau gene expression in an Alzheimer's disease model. The β-amyloid toxin was administered bilaterally into the hippocampus of Wistar male rats to induce Alzheimer's disease. The rats were then divided into four groups: the control group (which received distilled water as a solvent for β-amyloid toxin), the lesion group (which received the β-amyloid), β-amyloid + DMSO group (as antagonist solvent), and the AM251 antagonist receiving groups. During the training course of the Morris water maze test, the antagonist of the cannabinoid 1 receptor antagonist AM251 was administered bilaterally into the hippocampus for four consecutive days at doses of 5, 25, and 100 ng. To evaluate the spatial memory of the animals, the following parameters were analyzed: distance traveled, latency time to reach the hidden platform, velocity of the animals, and tau gene expression in real time. The spatial memory indices were found to be impaired following the injection of β-amyloid and the AM251 cannabinoid antagonist. Following the injection of β-amyloid toxin, there was an increase in mRNA expression of tau protein. However, no significant difference was observed between the cannabinoid antagonist and β-amyloid groups. These results indicate that β-amyloid toxin has a destructive effect on spatial memory and that cannabinoid system plays a positive role in memory formation and consolidation, However, further studies are needed to confirm these findings.

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来源期刊
Archives of Razi Institute
Archives of Razi Institute Veterinary-Veterinary (all)
CiteScore
1.50
自引率
0.00%
发文量
108
审稿时长
12 weeks
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