Zhang Yun, He Mao-Lin
Department of Neurology, Beijing Shijitan Hospital, Capital Medical University, 10 TieYi Rd, Haidian District, Beijing 100038, PR China.
Department of Neurology, Beijing Shijitan Hospital, Capital Medical University, 10 TieYi Rd, Haidian District, Beijing 100038, PR China.
Brain Res. 2017 Dec 15;1677:86-92. doi: 10.1016/j.brainres.2017.09.019. Epub 2017 Sep 27.
The neurotoxicity of amyloid-β peptide (Aβ), a predominant histopathological hallmark lesion of Alzheimer's disease (AD), is enhanced by iron, as found in amyloid plaques of Alzheimer's disease (AD) patients. We investigated whether deferoxamine (DFX) treatment promotes functional recovery and tissue repair in APP/PS1 double transgenic mice. Twelve-month-old APP/PS1 mice were randomly divided into two groups (APP/PS1 and DFX). Neurological deficits were monitored for 2weeks following DFX treatment. To characterize the activation of the microglia, expression of the M1 and M2 phenotypes was analyzed by immunohistochemistry and immunoblotting. Moreover, deposition of iron and Aβ, as well as apoptosis, were examined, and a behavioral test was performed. DFX significantly ameliorated cognitive function and deposition of Aβ as well as inhibited apoptosis in the brain. Consistent with these observations, DFX induced M2 activation of microglia and inhibited M1 activation of microglia in the hippocampus of APP/PS1 mice. In conclusion, DFX treatment improved functional recovery of AD mice, and the mechanism may involve DFX-induced M2 activation of microglia.
淀粉样β肽（Aβ）是阿尔茨海默病（AD）主要的组织病理学标志性病变，正如在AD患者的淀粉样斑块中所发现的那样，铁会增强其神经毒性。我们研究了去铁胺（DFX）治疗是否能促进APP/PS1双转基因小鼠的功能恢复和组织修复。将12月龄的APP/PS1小鼠随机分为两组（APP/PS1组和DFX组）。在DFX治疗后持续2周监测神经功能缺损情况。为了表征小胶质细胞的激活情况，通过免疫组织化学和免疫印迹分析M1和M2表型的表达。此外，检测了铁和Aβ的沉积以及细胞凋亡情况，并进行了行为测试。DFX显著改善了认知功能和Aβ的沉积，并抑制了大脑中的细胞凋亡。与这些观察结果一致，DFX诱导APP/PS1小鼠海马中小胶质细胞的M2激活，并抑制小胶质细胞的M1激活。总之，DFX治疗改善了AD小鼠的功能恢复，其机制可能涉及DFX诱导的小胶质细胞M2激活。
