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半乳糖寡糖可提高肌萎缩侧索硬化症 SOD1G93A 模型动物的存活率并减轻运动神经元死亡。

Galactooligosaccharide improves the animal survival and alleviates motor neuron death in SOD1G93A mouse model of amyotrophic lateral sclerosis.

机构信息

Institute of Neurology, Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, PR China.

出版信息

Neuroscience. 2013 Aug 29;246:281-90. doi: 10.1016/j.neuroscience.2013.05.002. Epub 2013 May 11.

DOI:10.1016/j.neuroscience.2013.05.002
PMID:23673277
Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disease caused by selective degeneration and death of motor neurons. So far very limited therapeutic options have emerged to treat this fatal disease. Homocysteine (Hcy) lowering drugs have been suggested to be a palliative therapy of this disease. Folate, Vitamin B12 (VitB12) and Vitamin B6 (VitB6) are important elements involved in the Hcy metabolism and we proposed that medications which could promote the absorption of folate, VitB12 and VitB6 might have benefit for ALS. Galactooligosaccharides (GOS) is a prebiotic which could significantly improve the absorption and syntheses of B Vitamins. To investigate whether GOS could provide neuroprotective effect in ALS, we applied GOS and GOS-rich prebiotic yogurt in SOD1(G93A) mice and assessed their effects on the disease progression of ALS. Our results showed that GOS and prebiotics yogurt administration significantly delayed the disease onset and prolonged the lifespan in SOD1(G93A) mice. Also, these products increased the concentration of folate, VitB12 and reduced the level of Hcy. Moreover, we found that both GOS and prebiotics yogurt attenuated motor neurons loss, improved the atrophy and mitochondrial activity in myocyte. Furthermore, we demonstrated that GOS and GOS-rich prebiotic treatment suppressed the activation of astrocytes and microglia and regulated several inflammatory- and apoptosis-related factors. Our findings suggested that GOS might have therapeutic potential for ALS, and GOS-rich prebiotic yogurt might be considered as a nutritional therapy for this disease.

摘要

肌萎缩侧索硬化症(ALS)是一种由运动神经元选择性变性和死亡引起的进行性和破坏性神经退行性疾病。到目前为止,已经出现了非常有限的治疗选择来治疗这种致命疾病。降低同型半胱氨酸(Hcy)的药物已被提议作为这种疾病的姑息治疗。叶酸、维生素 B12(VitB12)和维生素 B6(VitB6)是参与 Hcy 代谢的重要元素,我们提出能够促进叶酸、VitB12 和 VitB6 吸收的药物可能对 ALS 有益。半乳糖低聚糖(GOS)是一种益生元,可以显著改善 B 族维生素的吸收和合成。为了研究 GOS 是否可以在 ALS 中提供神经保护作用,我们在 SOD1(G93A)小鼠中应用 GOS 和富含 GOS 的益生元酸奶,并评估它们对 ALS 疾病进展的影响。我们的结果表明,GOS 和益生元酸奶的给药显著延迟了疾病的发作并延长了 SOD1(G93A)小鼠的寿命。此外,这些产品增加了叶酸、VitB12 的浓度并降低了 Hcy 的水平。此外,我们发现 GOS 和富含 GOS 的益生元酸奶均可减轻运动神经元的丢失,改善肌细胞的萎缩和线粒体活性。此外,我们证明 GOS 和富含 GOS 的益生元处理可抑制星形胶质细胞和小胶质细胞的激活,并调节几种与炎症和细胞凋亡相关的因子。我们的研究结果表明,GOS 可能对 ALS 具有治疗潜力,富含 GOS 的益生元酸奶可能被视为治疗这种疾病的营养疗法。

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