Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice.

Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice.
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DOI:
10.1186/1742-2094-9-197
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发表时间:
2012-08-13
影响因子:
9.3
通讯作者:
Fujino T
Fujino T
中科院分区:
医学1区
文献类型:
--
作者:
Ifuku M;Katafuchi T;Mawatari S;Noda M;Miake K;Sugiyama M;Fujino T

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神经炎症涉及阿尔茨海默病 (AD) 等神经退行性疾病中神经胶质细胞的激活。缩醛磷脂 (Pls) 是构成细胞膜的甘油磷脂,在膜流动性和细胞过程(例如囊泡融合和信号转导)中发挥重要作用。在本研究中,使用免疫组织化学、实时 PCR 方法和成年小鼠脑甘油磷脂水平分析,研究了 Pls 对全身脂多糖 (LPS) 诱导的神经炎症的预防作用。腹膜内 (i.p.) 注射 LPS (250 μg/kg) 7 天,导致前额皮质 (PFC) 和海马中 Iba-1 阳性小胶质细胞和胶质纤维酸性蛋白 (GFAP) 阳性星形胶质细胞数量增加,同时 IL-1β 和 TNF-α mRNA 表达增强。此外,注射 LPS 的动物的 PFC 和海马中出现了 β-淀粉样蛋白 (Aβ3-16) 阳性神经元。每天注射 LPS 后同时注射 Pls(腹腔注射,20 mg/kg)可显着减弱神经胶质细胞的活化和 Aβ 蛋白的积累。最后,注射 LPS 后,PFC 和海马中的 Pls 量减少,并且通过与 Pls 联合治疗抑制了这种减少。这些发现表明 Pls 具有抗神经炎症和抗淀粉样蛋白生成作用,从而表明 Pls 可以预防或治疗 AD。
Neuroinflammation involves the activation of glial cells in neurodegenerative diseases such as Alzheimer’s disease (AD). Plasmalogens (Pls) are glycerophospholipids constituting cellular membranes and play significant roles in membrane fluidity and cellular processes such as vesicular fusion and signal transduction. In this study the preventive effects of Pls on systemic lipopolysaccharide (LPS)-induced neuroinflammation were investigated using immunohistochemistry, real-time PCR methods and analysis of brain glycerophospholipid levels in adult mice. Intraperitoneal (i.p.) injections of LPS (250 μg/kg) for seven days resulted in increases in the number of Iba-1-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes in the prefrontal cortex (PFC) and hippocampus accompanied by the enhanced expression of IL-1β and TNF-α mRNAs. In addition, β-amyloid (Aβ3–16)-positive neurons appeared in the PFC and hippocampus of LPS-injected animals. The co-administration of Pls (i.p., 20 mg/kg) after daily LPS injections significantly attenuated both the activation of glial cells and the accumulation of Aβ proteins. Finally, the amount of Pls in the PFC and hippocampus decreased following the LPS injections and this reduction was suppressed by co-treatment with Pls. These findings suggest that Pls have anti-neuroinflammatory and anti-amyloidogenic effects, thereby indicating the preventive or therapeutic application of Pls against AD.
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发表时间: 2003-01-01
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