Stromal cell-derived factor 1α decreases β-amyloid deposition in Alzheimer's disease mouse model
2012
Wang, Qi | Xu, Yi | Chen, Jin-Cao | Qin, Yuan-Yuan | Liu, Mao | Liu, Yang | Xie, Min-Jie | Yu, Zhi-Yuan | Zhu, Zhou | Wang, Wei
β-amyloid (Aβ) aggregates are known to induce neuronal and synaptic dysfunction, and thus are involved in learning and memory deficits in Alzheimer's disease (AD), making Aβ deposits a potential target for prevention or treatment. Microglia, especially bone marrow-derived microglia (BMDM), has been recently thought to play important roles in internalizing and phagocytozing Aβ. BMDM originate in the bone marrow, migrate into the blood as hematopoietic progenitor cells (HPCs) and enter the brain in a chemokine-dependent manner. An effective chemoattractant for HPCs is stromal cell-derived factor 1 (SDF-1), which is also involved in regulating HPCs differentiation. Therefore, we hypothesize that SDF-1 might have influence on the migration of BMDM from peripheral cycle to brain. To explore whether treatment with SDF-1α can decrease Aβ burden, APP/PS1 double transgenic mice were given intracerebroventricular injection of SDF-1α weekly from the age of 28 to 32weeks (4weeks of injections) or from 28 to 36weeks (8weeks of injections). The results of our study showed that SDF-1α treatment decreased the area and the number of Aβ deposits, increased the level of Iba-1, a marker of microglia, and increased the number of plaque associated microglia in the parenchyma of APP/PS1 transgenic mice. These results suggest that SDF-1 could provide a novel and promising target for the purpose of lowering Aβ pathology in AD.
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