Abstract | INTRODUCTION: 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.
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Authors | Bin Li, Maria E Gonzalez-Toledo, Chun-Shu Piao, Allen Gu, Roger E Kelley, Li-Ru Zhao |
Journal | Alzheimer's research & therapy
(Alzheimers Res Ther)
Vol. 3
Issue 2
Pg. 8
(Mar 15 2011)
ISSN: 1758-9193 [Electronic] England |
PMID | 21406112
(Publication Type: Journal Article)
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