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Protective effect of alpha-linoleic acid on Aβ-induced oxidative stress, neuroinflammation, and memory impairment by alteration of α7 nAChR and NMDAR gene expression in the hippocampus of rats
NeuroToxicology ( IF 3.4 ) Pub Date : 2021-06-07 , DOI: 10.1016/j.neuro.2021.06.002
Nahaleh Tofighi 1 , Masoumeh Asle-Rousta 1 , Mehdi Rahnema 1 , Rahim Amini 2
Affiliation  

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects many older people around the world. Numerous studies are underway to evaluate the protective effects of natural products in AD. Alpha-linoleic acid (ALA) is an essential unsaturated fatty acid that exhibits neuroprotective outcomes in rat models of ischemic stroke and Parkinson's disease. This research aimed to investigate the effect of ALA on oxidative stress, neuroinflammation, neuronal death, and memory deficit induced by amyloid-beta (Aβ) peptide. After intrahippocampal injection of Aβ1−42, rats received ALA (150 μg/kg, subcutaneously) for 14 consecutive days. ALA decreased the levels of malondialdehyde and nitric oxide, enhanced glutathione content, and increased the activity of catalase in the hippocampus of the rat model of AD. It also reduced the expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, nuclear factor-kappa B, and N-methyl-d-aspartate receptor subunits NR2A and NR2B mRNAs in the hippocampus, prevented the neuronal loss in the CA1 region, and enhanced the expression of α7 nicotinic acetylcholine receptor. In addition, ALA allowed Aβ1−42-injected rats to spend less time and distance to reach the hidden platform in the Morris water maze test and to swim longer in the target quadrant. We concluded that ALA reduces the biochemical, molecular, histological, and behavioral changes caused by Aβ1−42 and it may be an effective option for treating AD.



中文翻译:

α-亚油酸通过改变大鼠海马α7 nAChR和NMDAR基因表达对Aβ诱导的氧化应激、神经炎症和记忆障碍的保护作用

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病,影响着世界各地的许多老年人。许多研究正在进行以评估天然产物在 AD 中的保护作用。α-亚油酸 (ALA) 是一种必需的不饱和脂肪酸,在缺血性中风和帕金森病的大鼠模型中表现出神经保护作用。本研究旨在研究 ALA 对淀粉样蛋白-β (Aβ) 肽诱导的氧化应激、神经炎症、神经元死亡和记忆缺陷的影响。海马内注射 Aβ 1-42后,大鼠连续 14 天接受 ALA(150 μg/kg,皮下)。ALA降低了AD大鼠模型海马中丙二醛和一氧化氮的水平,提高了谷胱甘肽的含量,并增加了过氧化氢酶的活性。它还降低了海马中肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、核因子-kappa B和N-甲基-d-天冬氨酸受体亚基NR2A和NR2B mRNA的表达,防止了海马中的神经元丢失。 CA1 区,并增强 α7 烟碱型乙酰胆碱受体的表达。此外,ALA 允许 Aβ 1−42-被注射的老鼠花费更少的时间和距离到达莫里斯水迷宫测试中的隐藏平台,并在目标象限游得更久。我们得出结论,ALA 减少了由 Aβ 1-42引起的生化、分子、组织学和行为变化,它可能是治疗 AD 的有效选择。

更新日期:2021-06-11
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