PDF(Pubmed)
Abstract：
UNASSIGNED: The APP/PS1 mouse model recapitulates pathology of human Alzheimer\'s disease (AD). While amyloid-β peptide deposition and neurodegeneration are features of AD, the pathology may involve inflammation and impaired vascular regeneration.
UNASSIGNED: This study evaluated inflammatory environments in the brain and bone marrow (BM), and the impact on brain microvascular density.
UNASSIGNED: BM and frontal cortex from male nine-month-old APP/PS1 or the control C57Bl6/j mice were studied. Vascular density and inflammatory cells were evaluated in the sections of frontal cortex by immunohistochemistry. Different subsets of hematopoietic stem/progenitor cells (BM) and monocyte-macrophages were characterized by flow cytometry and by clonogenic assays. Myelopoietic or inflammatory factors were evaluated by real-time RT-PCR or by western blotting.
UNASSIGNED: CD34+ or CD31+ vascular structures were lower (p < 0.01, n = 6) in the frontal cortex that was associated with decreased number of Lin-Sca-1+cKit+ vasculogenic progenitor cells in the BM and circulation (p < 0.02, n = 6) compared to the control. Multipotent progenitor cells MPP4, common lymphoid, common myeloid and myeloid progenitor cells were higher in the APP/PS1-BM compared to the control, which agreed with increased numbers of monocytes and pro-inflammatory macrophages. The expression of pro-myelopoietic factors and alarmins was higher in the APP/PS1 BM-HSPCs or in the BM-supernatants compared to the control. Frontal cortices of APP/PS1 mice showed higher number of pro-inflammatory macrophages (CD11b+F4/80+ or CD80+) and microglia (OX42+Iba1+).
UNASSIGNED: These findings show that AD pathology in APP/PS1 mice is associated with upregulated myelopoiesis, which contributes to the brain inflammation and decreased vascularity.
UNASSIGNED: This study evaluated inflammatory environments in the brain and bone marrow (BM), and the impact on brain microvascular density.
UNASSIGNED: BM and frontal cortex from male nine-month-old APP/PS1 or the control C57Bl6/j mice were studied. Vascular density and inflammatory cells were evaluated in the sections of frontal cortex by immunohistochemistry. Different subsets of hematopoietic stem/progenitor cells (BM) and monocyte-macrophages were characterized by flow cytometry and by clonogenic assays. Myelopoietic or inflammatory factors were evaluated by real-time RT-PCR or by western blotting.
UNASSIGNED: CD34+ or CD31+ vascular structures were lower (p < 0.01, n = 6) in the frontal cortex that was associated with decreased number of Lin-Sca-1+cKit+ vasculogenic progenitor cells in the BM and circulation (p < 0.02, n = 6) compared to the control. Multipotent progenitor cells MPP4, common lymphoid, common myeloid and myeloid progenitor cells were higher in the APP/PS1-BM compared to the control, which agreed with increased numbers of monocytes and pro-inflammatory macrophages. The expression of pro-myelopoietic factors and alarmins was higher in the APP/PS1 BM-HSPCs or in the BM-supernatants compared to the control. Frontal cortices of APP/PS1 mice showed higher number of pro-inflammatory macrophages (CD11b+F4/80+ or CD80+) and microglia (OX42+Iba1+).
UNASSIGNED: These findings show that AD pathology in APP/PS1 mice is associated with upregulated myelopoiesis, which contributes to the brain inflammation and decreased vascularity.
摘要：
■APP/PS1小鼠模型概括了人类阿尔茨海默病(AD)的病理学。而淀粉样β肽沉积和神经变性是AD的特征,病理可能涉及炎症和受损的血管再生。
■这项研究评估了大脑和骨髓（BM）的炎症环境，以及对脑微血管密度的影响。
■研究了9个月大的雄性APP/PS1或对照C57Bl6/j小鼠的BM和额叶皮层。通过免疫组织化学评估额叶皮质切片中的血管密度和炎症细胞。通过流式细胞术和克隆形成测定法对造血干/祖细胞（BM）和单核细胞-巨噬细胞的不同亚群进行了表征。通过实时RT-PCR或蛋白质印迹法评估骨髓生成或炎症因子。
■额叶皮质中CD34+或CD31+血管结构较低(p<0.01,n=6),这与BM和循环中Lin-Sca-1+cKit+血管生成祖细胞的数量减少有关(p<0.02,n=6)。多能祖细胞MPP4，普通淋巴，APP/PS1-BM中常见的骨髓和骨髓祖细胞高于对照组，与单核细胞和促炎巨噬细胞数量增加一致。与对照相比，APP/PS1BM-HSPC或BM上清液中的促骨髓生成因子和警报因子的表达更高。APP/PS1小鼠的额叶皮质显示出较高数量的促炎巨噬细胞(CD11b+F4/80+或CD80+)和小胶质细胞(OX42+Iba1+)。
■这些发现表明APP/PS1小鼠的AD病理与骨髓生成上调有关，这有助于大脑炎症和血管减少。
■这项研究评估了大脑和骨髓（BM）的炎症环境，以及对脑微血管密度的影响。
■研究了9个月大的雄性APP/PS1或对照C57Bl6/j小鼠的BM和额叶皮层。通过免疫组织化学评估额叶皮质切片中的血管密度和炎症细胞。通过流式细胞术和克隆形成测定法对造血干/祖细胞（BM）和单核细胞-巨噬细胞的不同亚群进行了表征。通过实时RT-PCR或蛋白质印迹法评估骨髓生成或炎症因子。
■额叶皮质中CD34+或CD31+血管结构较低(p<0.01,n=6),这与BM和循环中Lin-Sca-1+cKit+血管生成祖细胞的数量减少有关(p<0.02,n=6)。多能祖细胞MPP4，普通淋巴，APP/PS1-BM中常见的骨髓和骨髓祖细胞高于对照组，与单核细胞和促炎巨噬细胞数量增加一致。与对照相比，APP/PS1BM-HSPC或BM上清液中的促骨髓生成因子和警报因子的表达更高。APP/PS1小鼠的额叶皮质显示出较高数量的促炎巨噬细胞(CD11b+F4/80+或CD80+)和小胶质细胞(OX42+Iba1+)。
■这些发现表明APP/PS1小鼠的AD病理与骨髓生成上调有关，这有助于大脑炎症和血管减少。
