Ghaiad Heba R, Nooh Mohammed M, El-Sawalhi Maha M, Shaheen Amira A
Biochemistry Department - Faculty of Pharmacy, Cairo University, Kasr el Ainy st., 11562, Cairo, Egypt.
Mol Neurobiol. 2017 Jul;54(5):3219-3229. doi: 10.1007/s12035-016-9891-5. Epub 2016 Apr 11.
Multiple sclerosis (MS) is a demyelinating neurodegenerative disease, representing a major cause of neurological disability in young adults. Resveratrol is a stilbenoid polyphenol, known to pass blood brain barrier and exhibit antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. Cuprizone model of MS is particularly beneficial in studying demyelination/remyelination. Our study examined the potential neuroprotective and pro-remyelination effects of resveratrol in cuprizone-intoxicated C57Bl/6 mice. Mice were fed with chow containing 0.7 % cuprizone for 7 days, followed by 3 weeks on 0.2 % cuprizone diet. Resveratrol (250 mg/kg/day, p.o.) was given for 3 weeks starting from the second week. At the end of the experiment, animals were tested on rotarod to evaluate changes in balance and motor coordination. Mice were then sacrificed to measure the brain content of glutathione, lipid peroxidation products, adenosine triphosphate, and phospho-inhibitory subunit of nuclear factor κB-α. The activities of cytochrome oxidase and superoxide dismutase were also assessed. The gene expression of myelin basic protein, 2',3'-cyclic nucleotide 3' phosphodiesterase, oligodendrocyte transcription factor-1 (Olig1), NF-κB p65 subunit, and tumor necrosis factor-α was also estimated. Luxol fast blue/periodic acid-Schiff stained brain sections were blindly scored to assess the myelin status. Resveratrol effectively enhanced motor coordination and balance, reversed cuprizone-induced demyelination, improved mitochondrial function, alleviated oxidative stress, and inhibited NF-κB signaling. Interestingly, resveratrol increased Olig1 expression that is positively correlated to active remyelination. The present study may be the first to indicate a pro-remyelinative effect for resveratrol which might represent a potential additive benefit in treating MS.
多发性硬化症（MS）是一种脱髓鞘性神经退行性疾病，是年轻成年人神经功能障碍的主要原因之一。白藜芦醇是一种芪类多酚，已知其能够通过血脑屏障，并在多种脑损伤中表现出抗氧化、抗炎和神经保护作用。MS的铜螯合剂模型在研究脱髓鞘/再髓鞘化方面特别有用。我们的研究考察了白藜芦醇对铜螯合剂中毒的C57Bl/6小鼠的潜在神经保护和促再髓鞘化作用。小鼠连续7天喂食含0.7%铜螯合剂的食物，随后3周喂食含0.2%铜螯合剂的食物。从第二周开始，给予白藜芦醇（250mg/kg/天，口服），持续3周。在实验结束时，对动物进行转棒试验以评估平衡和运动协调性的变化。然后处死小鼠，测量脑内谷胱甘肽、脂质过氧化产物、三磷酸腺苷和核因子κB-α磷酸化抑制亚基的含量。还评估了细胞色素氧化酶和超氧化物歧化酶的活性。此外，还估计了髓鞘碱性蛋白、2',3'-环核苷酸3'磷酸二酯酶、少突胶质细胞转录因子-1（Olig1）、NF-κB p65亚基和肿瘤坏死因子-α的基因表达。对Luxol固蓝/过碘酸-希夫染色的脑切片进行盲法评分，以评估髓鞘状态。白藜芦醇有效地增强了运动协调性和平衡能力，逆转了铜螯合剂诱导的脱髓鞘，改善了线粒体功能，减轻了氧化应激，并抑制了NF-κB信号传导。有趣的是，白藜芦醇增加了与活跃再髓鞘化呈正相关的Olig1表达。本研究可能首次表明白藜芦醇具有促再髓鞘化作用，这可能是治疗MS的潜在附加益处。
