Yang Hui, Yue Caibin, Yang Hongna, Xie Zhaohong, Hu Hongzhen, Wei Lifei, Wang Ping, Zhao Cuiping, Bi Jianzhong
Department of Neurology Medicine, Second Hospital of Shandong University, Jinan, 250033, People's Republic of China.
Neurochem Res. 2013 Sep 29. doi: 10.1007/s11064-013-1161-6.
Alzheimer's disease (AD) is characterized by Amyloid-β (Aβ) deposition in senile plaques in specific areas of the brain and by intraneuronal p-tau accumulation in neurofibrillary tangles. Cumulative evidence supports that oxidative stress is an important factor in the pathogenesis of AD and contributes to Aβ generation. However, there is no effective treatment for AD. Human umbilical cord mesenchymal stem cells (HUMSCs) have potential therapeutic value for the treatment of neurological disease. However, the therapeutic impact of systemic administration of HUMSCs and their mechanism of action in AD have not yet been determined. Here, we found that intravenous infusion of HUMSCs significantly improved spatial learning and alleviated memory decline in an AβPP/PS1 mouse model of AD. HUMSC treatment also increased glutathione (GSH) activity and ratio of GSH to oxidative glutathione as well as superoxide dismutase activity, while decreasing malondialdehyde activity and protein carbonyl level, which suggests that HUMSC infusion alleviated oxidative stress in AβPP/PS1 mice. In addition, HUMSC infusion reduced β-secretase 1 and CTFβ, thus reducing Aβ deposition in mice. HUMSCs may have beneficial effects in the prevention and treatment of AD.
阿尔茨海默病(AD)的特征是大脑特定区域的老年斑中存在淀粉样β蛋白(Aβ)沉积以及神经原纤维缠结中存在神经元内磷酸化tau蛋白积累。越来越多的证据支持氧化应激是AD发病机制中的一个重要因素,并促成Aβ的生成。然而,目前尚无针对AD的有效治疗方法。人脐带间充质干细胞(HUMSCs)对神经系统疾病的治疗具有潜在的治疗价值。然而,全身给予HUMSCs的治疗效果及其在AD中的作用机制尚未确定。在此,我们发现静脉输注HUMSCs可显著改善AβPP/PS1 AD小鼠模型的空间学习能力并减轻记忆衰退。HUMSC治疗还增加了谷胱甘肽(GSH)活性、GSH与氧化型谷胱甘肽的比率以及超氧化物歧化酶活性,同时降低了丙二醛活性和蛋白质羰基水平,这表明输注HUMSCs减轻了AβPP/PS1小鼠的氧化应激。此外,输注HUMSCs降低了β-分泌酶1和CTFβ,从而减少了小鼠体内的Aβ沉积。HUMSCs可能对AD的预防和治疗具有有益作用。