Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice

粒细胞-巨噬细胞集落刺激因子对阿尔茨海默病小鼠的神经保护作用

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作者:Tomomi Kiyota, Jatin Machhi, Yaman Lu, Bhagyalaxmi Dyavarshetty, Maryam Nemati, Izumi Yokoyama, R L Mosley, Howard E Gendelman

Abstract

We investigated the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on behavioral and pathological outcomes in Alzheimer's disease (AD) and non-transgenic mice. GM-CSF treatment in AD mice reduced brain amyloidosis, increased plasma Aβ, and rescued cognitive impairment with increased hippocampal expression of calbindin and synaptophysin and increased levels of doublecortin-positive cells in the dentate gyrus. These data extend GM-CSF pleiotropic neuroprotection mechanisms in AD and include regulatory T cell-mediated immunomodulation of microglial function, Aβ clearance, maintenance of synaptic integrity, and induction of neurogenesis. Together these data support further development of GM-CSF as a neuroprotective agent for AD.

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