Alzheimer＇s disease（AD） is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta（Aβ） peptide in human brains. Oxidative stress and...Alzheimer＇s disease（AD） is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta（Aβ） peptide in human brains. Oxidative stress and neuroinflammation induced by Aβ in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Aβ25-35 in vivo. Briefly, the AD model was induced by injecting Aβ25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides（200, 400 and 800 mg/kg, p.o.） for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase（SOD）, glutathione（GSH）, acetylcholine esterase（ACh E）, and the content of malondialdehyde（MDA） as well as the level of nitric oxide（NO） in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2＇-deoxyguanosine（8-OHd G）, tumor necrosis factor-α（TNF-α）, interleukin 1β（IL-1β） and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase（i NOS） and nuclear factor κB（NF-κB） were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides（400 or 800 mg/kg）. All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system.展开更多
目的:探讨海马内注射β-amyloid protein 25-35(Aβ25-35)所致Alzheizer’s病(AD)模型大鼠空间学习记忆功能障碍的海马突触可塑性长时程增强(LTP)机制,为联合开展AD动物行为学和在体电生理学研究提供实验证据。方法:在脑立体定位仪上给...目的:探讨海马内注射β-amyloid protein 25-35(Aβ25-35)所致Alzheizer’s病(AD)模型大鼠空间学习记忆功能障碍的海马突触可塑性长时程增强(LTP)机制,为联合开展AD动物行为学和在体电生理学研究提供实验证据。方法:在脑立体定位仪上给予大鼠双侧海马分别注射4 nmol/L Aβ25-35或等体积生理盐水每侧2μl,手术后恢复2周,每只大鼠依次进行行为学和电生理两部分实验。首先,利用Morris水迷宫进行空间学习、记忆功能测试;之后,进行在体海马CA1区场兴奋性突触后电位(fEPSP)引导记录实验,观察突触可塑性指标长时程增强(LTP)的改变。结果:与对照组相比,海马内注射Aβ25-35大鼠的空间学习记忆功能和在体海马突触可塑性LTP均有改变,其中:逃避潜伏期和逃避距离明显增加(P<0.01);目标象限内游泳时间和距离明显缩短(P<0.01);在体海马LTP幅度显著降低(P<0.01)。结论:海马内注射Aβ25-35可导致大鼠空间学习记忆功能障碍;联合实验中Aβ25-35同样可引起在体海马LTP改变。提示同批动物先后进行行为学和电生理学测试的方法是可行的,行为学实验不会影响后续LTP的实验结果。因此,本实验为行为学改变后进行在体LTP机制探讨提供了实验依据,为有效开展行为学和电生理学实验提供了思路。展开更多
基金supported by the grants from the National Nature Science Foundation of China(No.81173065)Wuhan Science and Technology Plan Foundation(No.2012605-23182)
文摘Alzheimer＇s disease（AD） is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta（Aβ） peptide in human brains. Oxidative stress and neuroinflammation induced by Aβ in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Aβ25-35 in vivo. Briefly, the AD model was induced by injecting Aβ25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides（200, 400 and 800 mg/kg, p.o.） for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase（SOD）, glutathione（GSH）, acetylcholine esterase（ACh E）, and the content of malondialdehyde（MDA） as well as the level of nitric oxide（NO） in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2＇-deoxyguanosine（8-OHd G）, tumor necrosis factor-α（TNF-α）, interleukin 1β（IL-1β） and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase（i NOS） and nuclear factor κB（NF-κB） were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides（400 or 800 mg/kg）. All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system.
文摘目的:探讨海马内注射β-amyloid protein 25-35(Aβ25-35)所致Alzheizer’s病(AD)模型大鼠空间学习记忆功能障碍的海马突触可塑性长时程增强(LTP)机制,为联合开展AD动物行为学和在体电生理学研究提供实验证据。方法:在脑立体定位仪上给予大鼠双侧海马分别注射4 nmol/L Aβ25-35或等体积生理盐水每侧2μl,手术后恢复2周,每只大鼠依次进行行为学和电生理两部分实验。首先,利用Morris水迷宫进行空间学习、记忆功能测试;之后,进行在体海马CA1区场兴奋性突触后电位(fEPSP)引导记录实验,观察突触可塑性指标长时程增强(LTP)的改变。结果:与对照组相比,海马内注射Aβ25-35大鼠的空间学习记忆功能和在体海马突触可塑性LTP均有改变,其中:逃避潜伏期和逃避距离明显增加(P<0.01);目标象限内游泳时间和距离明显缩短(P<0.01);在体海马LTP幅度显著降低(P<0.01)。结论:海马内注射Aβ25-35可导致大鼠空间学习记忆功能障碍;联合实验中Aβ25-35同样可引起在体海马LTP改变。提示同批动物先后进行行为学和电生理学测试的方法是可行的,行为学实验不会影响后续LTP的实验结果。因此,本实验为行为学改变后进行在体LTP机制探讨提供了实验依据,为有效开展行为学和电生理学实验提供了思路。
