Spermidine Alleviates Severity of Murine Experimental Autoimmune Encephalomyelitis
Spermidine Alleviates Severity of Murine Experimental Autoimmune Encephalomyelitis
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DOI：
10.1167/iovs.10-6015
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Harada, Takayuki
中科院分区：
文献类型：
--
作者：
Guo, Xiaoli;Harada, Chikako;Harada, Takayuki
目的.评估亚精胺对多发性硬化（MS）动物模型实验性自身免疫性脑脊髓炎（EAE）严重程度的影响，重点关注常与MS和EAE相关的视神经炎。髓鞘少突胶质细胞糖蛋白诱导的EAE小鼠与或不与亚精胺在30 mM的饮用水中给药25天。每天对EAE的临床体征进行评分，并通过多焦视网膜电图测量视功能。在第25天处死小鼠后进行脊髓和视神经的组织学分析。使用探针2 '-7'二氯荧光素二乙酸酯（DCFDA）检测视神经中的过氧化氢（H2 O2）。采用乳酸脱氢酶法观察亚精胺对H2 O2诱导的视网膜神经节细胞凋亡的影响。每日临床评分显示，亚精胺治疗组EAE的严重程度显着减弱，亚精胺治疗小鼠脊髓中轻度脱髓鞘和轴突存活改善证实了这一点。与溶剂处理的小鼠相比，亚精胺处理的小鼠的视觉功能显著改善。亚精胺治疗改善了视神经脱髓鞘的程度，并防止了视网膜神经节细胞层的细胞丢失。此外，亚精胺处理的EAE小鼠的视神经中发现了较少的DCFDA标记细胞，并且体外分析显示亚精胺减少了H2 O2诱导的视网膜神经节细胞凋亡，表明亚精胺作为抗氧化剂减轻了EAE的严重程度，特别是视神经炎。这项研究的结果表明，口服亚精胺给药可能是MS的有效治疗方法（Invest Ophthalmol维斯科学。2011;52：2696-2703）DOI：10.1167/iovs.10-6015
PURPOSE. To assess the effects of spermidine on the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), with a focus on optic neuritis often associated with MS and EAE.METHODS. Myelin oligodendrocyte glycoprotein-induced EAE mice were administered with or without spermidine at 30 mM in drinking water for 25 days. Clinical signs of EAE were scored daily, and visual functions were measured by multifocal electroretinograms. Histopathology analysis of the spinal cord and optic nerve was performed after mice were killed on day 25. Hydrogen peroxide (H2O2) was detected using the probe 2'-7' dichlorofluorescein diacetate (DCFDA) in the optic nerve. The effect of spermidine on H2O2-induced retinal ganglion cell apoptosis was investigated by lactate dehydrogenase assay.RESULTS. Daily clinical scoring revealed that the severity of EAE was significantly attenuated in the spermidine-treated group, which was confirmed by milder demyelination and improved axon survival in the spinal cord of spermidine-treated mice. Visual functions were significantly improved in spermidine-treated mice compared with vehicle-treated mice. Spermidine treatment ameliorated the extent of demyelination in the optic nerve and prevented cell loss in the retinal ganglion cell layer. Furthermore, fewer DCFDA-labeled cells were found in the optic nerve in the spermidine-treated EAE mice, and in vitro analysis revealed that spermidine reduced H2O2-induced retinal ganglion cell apoptosis, suggesting that spermidine alleviated the severities of EAE, particularly of optic neuritis, by acting as an antioxidant.CONCLUSIONS. The results from this study suggest that oral spermidine administration could be a useful treatment for MS. (Invest Ophthalmol Vis Sci. 2011;52:2696-2703) DOI:10.1167/iovs.10-6015