Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis.
Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis.
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DOI：
10.3389/fneur.2012.00084
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发表时间：
2012
影响因子：
3.4
通讯作者：
Shindler KS
中科院分区：
文献类型：
--
作者：
Fonseca-Kelly Z;Nassrallah M;Uribe J;Khan RS;Dine K;Dutt M;Shindler KS
白藜芦醇是一种天然存在的多酚，可以激活SIRT1，一种nadd依赖性去乙酰化酶。SRT501是一种增强全身吸收的白藜芦醇药物制剂，在多发性硬化症（MS）模型复发性实验性自身免疫性脑脊髓炎（EAE）小鼠中防止神经元丢失而不抑制炎症。相比之下，据报道白藜芦醇可以抑制慢性EAE的炎症反应，但神经保护作用尚未得到评估。本研究探讨了白藜芦醇对C57/Bl6小鼠髓鞘少突胶质糖蛋白肽免疫诱导的慢性EAE的潜在神经保护和免疫调节作用。比较了每日口服两种不同白藜芦醇制剂的效果。白藜芦醇延缓了EAE小鼠的发作，但没有阻止或改变脊髓或视神经炎症的表型。观察到显著的神经保护作用，白藜芦醇处理的视神经炎症EAE小鼠的眼睛中发现更多的视网膜神经节细胞。结果表明，白藜芦醇可以防止这种慢性脱髓鞘疾病模型中的神经元丢失，其作用与复发性EAE相似。与先前的研究相比，免疫抑制的差异表明免疫调节作用可能是有限的，可能取决于特定的免疫参数或治疗时间。重要的是，神经保护作用可以在没有免疫抑制的情况下发生，这表明白藜芦醇与抗炎疗法联合治疗多发性硬化症有潜在的附加益处。
Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for MS.