Tofighi Nahaleh, Asle-Rousta Masoumeh, Rahnema Mehdi, Amini Rahim
Department of Physiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Department of Physiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Neurotoxicology. 2021 Jul;85:245-253. doi: 10.1016/j.neuro.2021.06.002. Epub 2021 Jun 7.
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 Aβ, 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 Aβ-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 Aβ and it may be an effective option for treating AD.
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。目前正在进行大量研究以评估天然产物对AD的保护作用。α-亚麻酸（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。本研究旨在探讨ALA对淀粉样β蛋白（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。在海马内注射Aβ后，大鼠连续14天接受ALA（150μg/kg，皮下注射）。ALA降低了丙二醛和一氧化氮水平，提高了谷胱甘肽含量，并增加了AD大鼠模型海马中过氧化氢酶的活性。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-κB以及N-甲基-D-天冬氨酸受体亚基NR2A和NR2B mRNA的表达，防止了CA1区的神经元丢失，并增强了α7烟碱型乙酰胆碱受体的表达。此外，在莫里斯水迷宫试验中，ALA使注射Aβ的大鼠到达隐藏平台的时间和距离缩短，并在目标象限中游泳的时间延长。我们得出结论，ALA减少了由Aβ引起的生化、分子、组织学和行为变化，它可能是治疗AD的一种有效选择。
