Chitosan oligosaccharides alleviate cognitive deficits in an amyloid-β1-42-induced rat model of Alzheimer's disease
Chitosan oligosaccharides alleviate cognitive deficits in an amyloid-β1-42-induced rat model of Alzheimer's disease
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DOI：
10.1016/j.ijbiomac.2015.11.011
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发表时间：
2016-02-01
影响因子：
8.2
通讯作者：
Sun, Yaxuan
中科院分区：
文献类型：
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作者：
Jia, Shiliang;Lu, Zheng;Sun, Yaxuan
目的：方法：采用Morris水迷宫和被动回避实验，观察壳寡糖（chitosan oligosaccharides，COS）对A β（1-42）诱导的大鼠学习记忆障碍的保护作用。结果：口服200、400、800 mg/kg剂量的COS能有效地减轻A β（1-42）诱导的大鼠学习记忆障碍。这些相同的剂量也能够改善神经元凋亡。COS的神经保护作用与其抑制氧化应激的能力密切相关。这表现为丙二醛、8-羟基-2 '-脱氧鸟苷水平降低，谷胱甘肽过氧化物酶和超氧化物歧化酶活性水平升高。COS还显示通过减少促炎细胞因子的释放来抑制炎症反应并减少炎症的测量结论：总的来说，我们的研究结果表明COS通过抑制氧化应激和神经炎症反应对A β（1-42）诱导的阿尔茨海默病模型中的认知障碍具有有益的作用。(C)2015爱思唯尔B. V.保留所有权利。
Aim: The objective of the present study was two-fold: (i) to evaluate the modulating effects of chitosan oligosaccharides (COS) on cognitive deficits and (ii) to explore their underlying molecular mechanisms.Methods: The Morris water maze and passive avoidance tests were used to determine the neuroprotective effects of COS on A beta(1-42)-induced learning and memory impairments. Biochemical methods were then used to assess COS antioxidant activity in hippocampus, including effects on apoptosis (TUNEL assay) and changes in inflammatory mediators (immunohistochemistry).Results: Orally administered COS at 200, 400, or 800 mg/kg doses were effective at reducing the learning and memory deficits in A beta(1-42)-induced rats. These same doses were also able to ameliorate neuronal apoptosis. The neuroprotective effects of COS were closely associated with its ability to inhibit oxidative stress. This was shown with decreasing levels of malondialdehyde, 8-hydroxy-2'-deoxyguanosine and increasing levels of glutathione peroxidase and super oxide dismutase activities. COS were also shown to suppress the inflammatory response and decrease measures of inflammation via a decrease in the release of proinflammatory cytokines (e.g. interleukin-1beta and tumor necrosis factor-alpha).Conclusion: Taken together, our findings suggest that COS have beneficial effects on the cognitive impairments seen in an A beta(1-42)-induced model of Alzheimer's disease via inhibiting oxidative stress and neuroinflammatory responses. (C) 2015 Elsevier B.V. All rights reserved.