RRC ID 68992
Author Liu X, Zhou Q, Zhang JH, Wang KY, Saito T, Saido TC, Wang X, Gao X, Azuma K.
Title Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer's Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin.
Journal Cells
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.
Volume 10(11)
Published 2021-11-22
DOI 10.3390/cells10113261
PII cells10113261
PMID 34831483
PMC PMC8625413
MeSH Alzheimer Disease / drug therapy* Alzheimer Disease / pathology* Amyloid beta-Protein Precursor / metabolism Animals Body Weight / drug effects Brain / drug effects Brain / pathology* Brain / ultrastructure Cytokines / metabolism Diosgenin / analogs & derivatives* Diosgenin / pharmacology Diosgenin / therapeutic use Disease Models, Animal Female Male Mice, Inbred C57BL Mice, Transgenic Microglia / pathology* Models, Biological NF-kappa B / metabolism Sex Characteristics* Signal Transduction Synapses / drug effects Synapses / pathology Synapses / ultrastructure beta Catenin / metabolism
IF 4.366
Mice RBRC06344