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Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
- Source :
- Cells, Vol 10, Iss 11, p 3261 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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.
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 10
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0f374323079340529d0aaedd0f68f9b4
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/cells10113261