Premium
AAV2/1‐mediated gene delivery of CD200 into the hippocampus enhances neurogenesis and amyloid clearance in the APP mouse
Author(s) -
Varnum Megan M,
Kiyota Tomomi,
Ingraham Kaitlin,
Ikezu Seiko,
Ikezu Tsuneya
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1177.2
Subject(s) - neurogenesis , neuroinflammation , dentate gyrus , microglia , neural stem cell , hippocampus , neurodegeneration , genetically modified mouse , neuroscience , amyloid precursor protein , biology , transgene , microbiology and biotechnology , stem cell , alzheimer's disease , immunology , medicine , inflammation , disease , biochemistry , gene
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline of cognitive function and memory formation. Up‐regulation of inflammatory cytokines, microglial activation, and toxic Aβ in the AD brain negatively affect the ability of neural stem cells to mature and survive. CD200 is an anti‐inflammatory glycoprotein expressed in many cell types, including neurons, and its receptor is expressed in myeloid cells, like microglia. It has been shown in AD patients and mouse models that an age‐related increase in microglial activation is accompanied by an age‐related or Aβ‐induced decrease in CD200. We hypothesize that chronic neuroinflammation in AD contributes to suppression of neurogenesis in the hippocampus, and that this suppression can be restored by gene delivery of CD200. In this study the AD transgenic (Tg) mouse model expressing an APP mutant was intrahippocampally injected with adeno‐associated virus expressing CD200 at the pre‐symptomatic disease stage. Following treatment with CD200, mice were assessed for Aβ load, and neurogenesis was measured. CD200 expression enhanced proliferation and differentiation of neural stem cells in the dentate gyrus and reduced Aβ load. These data indicate that CD200 may be able to delay the onset of AD‐like pathology and decrease in neurogenesis, thus giving it potential as a therapeutic against neurodegeneration. NIH 5T32GM008541 to MMV.