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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, Cells, Vol 10, Iss 3261, p 3261 (2021), Cells; Volume 10; Issue 11; Pages: 3261
- 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.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Alzheimer’s disease
AppNL-G-F
dioscin
amyloid-β
synaptic dysfunction
microglia
neuroinflammation
QH301-705.5
Hippocampus
Mice, Transgenic
Disease
Neuropathology
Diosgenin
Models, Biological
Article
Amyloid beta-Protein Precursor
Alzheimer Disease
medicine
Animals
Dementia
Biology (General)
Young adult
beta Catenin
Neuroinflammation
Sex Characteristics
Microglia
business.industry
Body Weight
NF-kappa B
Brain
General Medicine
medicine.disease
Cortex (botany)
Mice, Inbred C57BL
Disease Models, Animal
A ppNL-G-F
medicine.anatomical_structure
Synapses
Cytokines
Female
business
Signal Transduction
Subjects
Details
- ISSN :
- 20734409
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....8bf56ab0da9ff82e919699dfdbb7ab90