論文 - 詳細
| RRC ID | 68992 |
|---|---|
| 著者 | Liu X, Zhou Q, Zhang JH, Wang KY, Saito T, Saido TC, Wang X, Gao X, Azuma K. |
| タイトル | Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer's Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin. |
| ジャーナル | 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. |
| 巻・号 | 10(11) |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC06344 |