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- Title
Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer's Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin.
- Authors
Liu, Xiao; Zhou, Qian; Zhang, Jia-He; Wang, Ke-Yong; Saito, Takashi; Saido, Takaomi C.; Wang, Xiaoying; Gao, Xiumei; Azuma, Kagaku
- Abstract
Alzheimer's disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.
- Subjects
ALZHEIMER'S disease; ANIMAL disease models; LABORATORY mice; MICROGLIA; MEDICAL model; CELLULAR signal transduction; YOUNG adults; MICE; PATHOLOGIC neovascularization
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 11, p3261
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10113261