Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APP/PS1 transgenic mice.
Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APP/PS1 transgenic mice.
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DOI：
10.1186/alzrt67
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发表时间：
2011-03-15
期刊：
影响因子：
--
通讯作者：
Zhao LR
中科院分区：
文献类型：
--
作者：
Li B;Gonzalez-Toledo ME;Piao CS;Gu A;Kelley RE;Zhao LR
阿尔茨海默病（Alzheimer's disease，AD）是一种严重的公共卫生问题，也是一个沉重的经济负担。目前，没有治疗可以延迟或停止AD中的进行性脑损伤。最近，我们证明干细胞因子（SCF）联合粒细胞集落刺激因子（G-CSF）（SCF+G-CSF）对慢性脑卒中有治疗作用。本研究的目的是确定SCF+G-CSF是否可以减少AD小鼠模型中β-淀粉样蛋白沉积的负担。以APP/PS1转基因小鼠为AD模型。为了追踪脑中的骨髓来源细胞，用来自表达绿色荧光蛋白（GFP）的小鼠的骨髓替换APP/PS1小鼠的骨髓。骨髓移植后6周，将小鼠随机分为生理盐水对照组和SCF+G-CSF治疗组。SCF联合G-CSF皮下给药12天。在最后一次注射后1天定量循环骨髓干细胞（CD 117+细胞）。治疗后9个月，在18个月大时，处死小鼠。对脑切片进行免疫组织化学处理，以鉴定脑中β-淀粉样蛋白沉积物和表达GFP的骨髓来源的小胶质细胞。向APP/PS1转基因小鼠全身给予SCF+G-CSF导致脑中β-淀粉样蛋白沉积的长期减少。此外，我们还观察到SCF+G-CSF治疗增加了APP/PS1小鼠脑中的循环骨髓干细胞和骨髓来源的小胶质细胞。此外，SCF+G-CSF治疗导致骨髓来源的小胶质细胞和β-淀粉样蛋白沉积物在脑中的共定位增强。这些数据表明，骨髓来源的小胶质细胞在SCF+G-CSF诱导的减少β-淀粉样蛋白沉积的长期效应中发挥作用。本研究提供了造血生长因子SCF和G-CSF对限制AD中β-淀粉样蛋白积聚的贡献的见解，并可能为AD提供新的治疗方法。
Alzheimer's disease (AD) is widely recognized as a serious public health problem and heavy financial burden. Currently, there is no treatment that can delay or stop the progressive brain damage in AD. Recently, we demonstrated that stem cell factor (SCF) in combination with granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) has therapeutic effects on chronic stroke. The purpose of the present study is to determine whether SCF+G-CSF can reduce the burden of β-amyloid deposits in a mouse model of AD. APP/PS1 transgenic mice were used as the model of AD. To track bone marrow-derived cells in the brain, the bone marrow of the APP/PS1 mice was replaced with the bone marrow from mice expressing green fluorescent protein (GFP). Six weeks after bone marrow transplantation, mice were randomly divided into a saline control group and a SCF+G-CSF-treated group. SCF in combination with G-CSF was administered subcutaneously for 12 days. Circulating bone marrow stem cells (CD117+ cells) were quantified 1 day after the final injection. Nine months after treatment, at the age of 18 months, mice were sacrificed. Brain sections were processed for immunohistochemistry to identify β-amyloid deposits and GFP expressing bone marrow-derived microglia in the brain. Systemic administration of SCF+G-CSF to APP/PS1 transgenic mice leads to long-term reduction of β-amyloid deposition in the brain. In addition, we have also observed that the SCF+G-CSF treatment increases circulating bone marrow stem cells and augments bone marrow-derived microglial cells in the brains of APP/PS1 mice. Moreover, SCF+G-CSF treatment results in enhancement of the co-localization of bone marrow-derived microglia and β-amyloid deposits in the brain. These data suggest that bone marrow-derived microglia play a role in SCF+G-CSF-induced long-term effects to reduce β-amyloid deposits. This study provides insights into the contribution of the hematopoeitic growth factors, SCF and G-CSF, to limit β-amyloid accumulation in AD and may offer a new therapeutic approach for AD.
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