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在急性诱导的阿尔茨海默病小鼠模型中,骨髓间充质干细胞可减少脑内β-淀粉样蛋白沉积并加速小胶质细胞的激活。

Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer's disease mouse model.

作者信息

Lee Jong Kil, Jin Hee Kyung, Bae Jae-Sung

机构信息

Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, South Korea.

出版信息

Neurosci Lett. 2009 Jan 30;450(2):136-41. doi: 10.1016/j.neulet.2008.11.059. Epub 2008 Dec 6.

Abstract

The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has recently been explored in various pathological conditions of the central nervous system (CNS). However, the application of BM-MSCs in acutely induced Alzheimer's disease (AD) has not yet been reported. Herein the feasibility of using the BM-MSCs, as a therapeutic agent for AD has been tested. To assess this possibility, an acutely induced AD model induced by injecting amyloid-beta (Abeta) into the dentate gyrus (DG) of hippocampus of C57BL/6 mice was used. Intracerebral transplantation of BM-MSCs into the brain of an induced AD model reduced their Abeta levels when compared to sham-transplanted animals. The diminution of Abeta deposits was accompanied by the activation of microglia. In addition, the activated microglia was located near the Abeta deposits, and their morphology was changed from ramified to ameboid as a sign of microglial phagocytosis. This study provides evidence that BM-MSCs can promote the reduction of Abeta through the microglial activation in this acutely induced AD brain, suggesting a potential therapeutic agent against AD.

摘要

骨髓间充质干细胞(BM-MSCs)的治疗潜力最近在中枢神经系统(CNS)的各种病理状况中得到了探索。然而,BM-MSCs在急性诱导的阿尔茨海默病(AD)中的应用尚未见报道。在此,测试了使用BM-MSCs作为AD治疗剂的可行性。为评估这种可能性,使用了通过向C57BL/6小鼠海马齿状回(DG)注射β淀粉样蛋白(Aβ)诱导的急性AD模型。与假移植动物相比,将BM-MSCs脑内移植到诱导的AD模型脑中可降低其Aβ水平。Aβ沉积物的减少伴随着小胶质细胞的激活。此外,激活的小胶质细胞位于Aβ沉积物附近,其形态从分支状变为阿米巴样,这是小胶质细胞吞噬作用的标志。本研究提供了证据,表明BM-MSCs可通过在这种急性诱导的AD脑中激活小胶质细胞来促进Aβ的减少,提示其可能是一种抗AD的治疗剂。

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