干细胞因子和粒细胞集落刺激因子可减少 APP/PS1 转基因小鼠大脑中的 β-淀粉样蛋白沉积。
Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APP/PS1 transgenic mice.
机构信息
Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
出版信息
Alzheimers Res Ther. 2011 Mar 15;3(2):8. doi: 10.1186/alzrt67.
INTRODUCTION
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
简介
阿尔茨海默病（AD）是一个广泛公认的严重公共卫生问题和沉重的经济负担。目前，尚无治疗方法可以延缓或阻止 AD 中进行性的脑损伤。最近，我们证明了干细胞因子（SCF）与粒细胞集落刺激因子（G-CSF）（SCF+G-CSF）联合应用对慢性中风具有治疗作用。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。
方法
APP/PS1 转基因小鼠被用作 AD 模型。为了跟踪骨髓源性细胞在大脑中的情况，将 APP/PS1 小鼠的骨髓替换为表达绿色荧光蛋白（GFP）的小鼠的骨髓。骨髓移植 6 周后，将小鼠随机分为生理盐水对照组和 SCF+G-CSF 治疗组。SCF 与 G-CSF 联合皮下给药 12 天。最后一次注射后 1 天，定量检测循环骨髓干细胞（CD117+细胞）。治疗 9 个月后，在 18 个月龄时处死小鼠。对脑切片进行免疫组织化学处理，以鉴定大脑中的β-淀粉样蛋白沉积和 GFP 表达的骨髓源性小胶质细胞。
结果
SCF+G-CSF 全身给药可导致 APP/PS1 转基因小鼠大脑中的β-淀粉样蛋白沉积长期减少。此外，我们还观察到 SCF+G-CSF 治疗增加了 APP/PS1 小鼠的循环骨髓干细胞，并增加了大脑中的骨髓源性小胶质细胞。此外，SCF+G-CSF 治疗导致骨髓源性小胶质细胞与大脑中β-淀粉样蛋白沉积的共定位增强。
结论
这些数据表明，骨髓源性小胶质细胞在 SCF+G-CSF 诱导的长期减少β-淀粉样蛋白沉积的作用中发挥作用。该研究为造血生长因子 SCF 和 G-CSF 对限制 AD 中β-淀粉样蛋白积累的贡献提供了新的见解，并为 AD 提供了新的治疗方法。
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