Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer's Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin.
Cells
; 10(11)2021 11 22.
Article
em En
| MEDLINE
| ID: mdl-34831483
ABSTRACT
Alzheimer's disease (AD), the most common form of dementia, is characterized by amyloid-ß (Aß) 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-ß deposition, synaptic dysfunction, neuroinflammation, and dysregulation of ß-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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Caracteres Sexuais
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Microglia
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Diosgenina
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cells
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão