論文 - 詳細
| RRC ID | 87289 |
|---|---|
| 著者 | Wang T, Sobue A, Watanabe S, Komine O, Saido TC, Saito T, Yamanaka K. |
| タイトル | Dimethyl fumarate improves cognitive impairment and neuroinflammation in mice with Alzheimer's disease. |
| ジャーナル | J Neuroinflammation |
| Abstract |
BACKGROUND:Neuroinflammation substantially contributes to the pathology of Alzheimer's disease (AD), the most common form of dementia. Studies have reported that nuclear factor erythroid 2-related factor 2 (Nrf2) attenuates neuroinflammation in the mouse models of neurodegenerative diseases, however, the detailed mechanism remains unclear. METHODS:The effects of dimethyl fumarate (DMF), a clinically used drug to activate the Nrf2 pathway, on neuroinflammation were analyzed in primary astrocytes and AppNL-G-F (App-KI) mice. The cognitive function and behavior of DMF-administrated App-KI mice were evaluated. For the gene expression analysis, microglia and astrocytes were directly isolated from the mouse cerebral cortex by magnetic-activated cell sorting, followed by quantitative PCR. RESULTS:DMF treatment activated some Nrf2 target genes and inhibited the expression of proinflammatory markers in primary astrocytes. Moreover, chronic oral administration of DMF attenuated neuroinflammation, particularly in astrocytes, and reversed cognitive dysfunction presumably by activating the Nrf2-dependent pathway in App-KI mice. Furthermore, DMF administration inhibited the expression of STAT3/C3 and C3 receptor in astrocytes and microglia isolated from App-KI mice, respectively, suggesting that the astrocyte-microglia crosstalk is involved in neuroinflammation in mice with AD. CONCLUSION:The activation of astrocytic Nrf2 signaling confers neuroprotection in mice with AD by controlling neuroinflammation, particularly by regulating astrocytic C3-STAT3 signaling. Furthermore, our study has implications for the repositioning of DMF as a drug for AD treatment. |
| 巻・号 | 21(1) |
| ページ | 55 |
| 公開日 | 2024-2-21 |
| DOI | 10.1186/s12974-024-03046-2 |
| PII | 10.1186/s12974-024-03046-2 |
| PMID | 38383481 |
| PMC | PMC10882778 |
| MeSH | Alzheimer Disease* / complications Alzheimer Disease* / drug therapy Alzheimer Disease* / genetics Animals Cognitive Dysfunction* / drug therapy Cognitive Dysfunction* / etiology Dimethyl Fumarate / pharmacology Dimethyl Fumarate / therapeutic use Disease Models, Animal Mice Mice, Transgenic NF-E2-Related Factor 2 / metabolism Neuroinflammatory Diseases |
| リソース情報 | |
| 実験動物マウス | RBRC01390 |