論文 - 詳細
| RRC ID | 63808 |
|---|---|
| 著者 | Gu Y, Wu Z, Zeng F, Jiang M, Teeling JL, Ni J, Takahashi I. |
| タイトル | Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis Induces Bone Loss-Correlated Alzheimer's Disease-Like Pathologies in Middle-Aged Mice. |
| ジャーナル | J Alzheimers Dis |
| Abstract |
BACKGROUND:Alzheimer's disease (AD) and bone loss are clinically exacerbated. However, the mechanism of exacerbation remains understood. OBJECTIVE:We tested our hypothesis that periodontitis is involved in the exacerbation, contributing to AD pathologies. METHODS:The bone, memory, and inflammation in bone and brain were examined in 12-month-old mice after systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (P gLPS) for 3 consecutive weeks. RESULTS:Compared with control mice, bone loss in tibia (26% decrease) and memory decline (47% decrease) were induced in mice with a positive correlation after exposure to P gLPS (r = 0.7378, p = 0.0011). The IL-6 and IL-17 expression in tibia was negatively correlated with the bone volume/total tissue volume (r = -0.6619, p = 0.0052; r = -0.7129, p = 0.0019), while that in the cortex was negatively correlated with the memory test latency (r = -0.7198, p = 0.0017; p = 0.0351, r = -0.5291). Furthermore, the IL-17 expression in microglia was positively correlated with Aβ42 accumulation in neurons (r = 0.8635, p < 0.0001). In cultured MG6 microglia, the P gLPS-increased IL-6 expression was inhibited by a PI3K-specific inhibitor (68% decrease), and that of IL-17 was inhibited by IL-6 antibody (41% decrease). In cultured N2a neurons, conditioned medium from P gLPS-stimulated microglia (MCM) but not P gLPS increased the productions of AβPP, CatB, and Aβ42, which were significantly inhibited by pre-treatment with IL-17 antibody (67%, 51%, and 41% decrease). CONCLUSION:These findings demonstrated that chronic systemic exposure to P gLPS simultaneously induces inflammation-dependent bone loss and AD-like pathologies by elevating IL-6 and IL-17 from middle age, suggesting that periodontal bacteria induce exacerbation of bone loss and memory decline, resulting in AD progression. |
| 巻・号 | 78(1) |
| ページ | 61-74 |
| 公開日 | 2020-1-1 |
| DOI | 10.3233/JAD-200689 |
| PII | JAD200689 |
| PMID | 32925065 |
| MeSH | Alzheimer Disease / microbiology* Animals Disease Models, Animal Female Inflammation / metabolism Interleukin-17 Lipopolysaccharides* Mice Mice, Inbred C57BL Microglia / metabolism Neurons / metabolism Periodontitis / microbiology Porphyromonas gingivalis* Tibia / microbiology |
| IF | 3.909 |
| リソース情報 | |
| ヒト・動物細胞 | MG6(RCB2403) |