The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:36

Article

Varnum, Megan M.¹  Kiyota, Tomomi²  Ingraham, Kaitlin L.¹  Ikezu, Seiko¹  Ikezu, Tsuneya^1,3 

[1] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA

[2] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA

[3] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

关键词: Alzheimer's disease;    Microglia;    Adeno-associated virus;    Neuroinflammation;    Transgenic mouse model;    CD200;   

DOI  :  10.1016/j.neurobiolaging.2015.07.027

来源: Elsevier

【 摘 要 】

Cluster of Differentiation-200 (CD200) is an anti-inflammatory glycoprotein expressed in neurons, T cells, and B cells, and its receptor is expressed on glia. Both Alzheimer's disease patients and mouse models display age-related or amyloid-beta peptide (A beta)-induced reductions in CD200. The goal of this study was to determine if neuronal CD200 expression restores hippocampal neurogenesis and reduces A beta in the amyloid precursor protein mouse model. Amyloid precursor protein and wild-type mice were injected at 6 months of age with an adeno-associated virus expressing CD200 into the hippocampus and sacrificed at 12 months. CD200 expression restored neural progenitor cell proliferation and differentiation in the subgranular and granular cell layers of the dentate gyrus and reduced diffuse but not thioflavin-S+ plaques in the hippocampus. In vitro studies demonstrated that CD200-stimulated microglia increased neural differentiation of neural stem cells and enhanced axon elongation and dendrite number. CD200 also enhanced A beta uptake by microglia. These data indicate that CD200 is capable of enhancing microglia-mediated A beta clearance and neural differentiation and has potential as a therapeutic for Alzheimer's disease. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

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