Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
J Neuroinflammation. 2012 Aug 13;9:197. doi: 10.1186/1742-2094-9-197.
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.
神经炎症涉及神经退行性疾病(如阿尔茨海默病(AD))中神经胶质细胞的激活。溶血磷脂(Pls)是构成细胞膜的甘油磷脂,在膜流动性和细胞过程(如囊泡融合和信号转导)中发挥重要作用。
本研究采用免疫组织化学、实时 PCR 方法和脑甘油磷脂水平分析,研究了 Pls 对成年小鼠系统性脂多糖(LPS)诱导的神经炎症的预防作用。
腹腔内(i.p.)注射 LPS(250μg/kg)连续 7 天可增加前额叶皮层(PFC)和海马中 Iba-1 阳性小胶质细胞和胶质纤维酸性蛋白(GFAP)阳性星形胶质细胞的数量,同时增强 IL-1β 和 TNF-α mRNA 的表达。此外,LPS 注射动物的 PFC 和海马中出现β-淀粉样蛋白(Aβ3-16)阳性神经元。每日 LPS 注射后给予 Pls(i.p.,20mg/kg)共同给药可显著减轻神经胶质细胞的激活和 Aβ 蛋白的积累。最后,LPS 注射后 PFC 和海马中的 Pls 含量减少,而 Pls 共同治疗可抑制这种减少。
这些发现表明 Pls 具有抗炎和抗淀粉样蛋白形成作用,从而表明 Pls 对 AD 的预防或治疗应用。