Lack of Alpha-Synuclein Modulates Microglial Phenotype In Vitro
Lack of Alpha-Synuclein Modulates Microglial Phenotype In Vitro
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DOI：
10.1007/s11064-011-0439-9
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发表时间：
2011-06-01
影响因子：
4.4
通讯作者：
Combs, Colin K.
中科院分区：
文献类型：
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作者：
Austin, Susan A.;Rojanathammanee, Lalida;Combs, Colin K.
α (α)-突触核蛋白神经元效应不断被定义，尽管其在调节神经胶质表型中的作用仍不清楚。利用野生型和α -突触核蛋白缺陷小鼠（Snca(-/-)）的原代培养物研究了调节小胶质细胞激活的能力。与野生型细胞相比，Snca（-/-）小胶质细胞表现出细胞因子肿瘤坏死因子- α (tnf - α)分泌增加，吞噬能力受损，前列腺素水平升高，脂质介导的信号事件中关键酶的蛋白水平升高，胞质磷脂酶（cPLA(2)），环氧化酶-2 （Cox-2）和磷脂酶D2 （PLD2）。通过正丁醇处理抑制pld依赖性信号传导，Snca（-/-）小胶质细胞中增加的细胞因子分泌和cPLA(2)和Cox-2水平部分减弱。
Alpha (alpha)-synuclein neuronal effects are continually being defined although its role in regulating glial phenotypes remains unclear. An ability to regulate microglial activation was investigated using primary cultures from wild type and alpha-synuclein deficient mice (Snca (-/-)). Snca (-/-) microglia demonstrated increased secretion of the cytokine tumor necrosis factor-alpha (TNF-alpha), impaired phagocytic ability, elevated prostaglandin levels, and increased protein levels of key enzymes in lipid-mediated signaling events, cytosolic phospholipase (cPLA(2)), cyclooxygenase-2 (Cox-2) and phospholipase D2 (PLD2) when compared to wild type cells. Increased cytokine secretion and cPLA(2) and Cox-2 levels in Snca (-/-) microglia were partially attenuated by inhibiting PLD-dependent signaling with n-butanol treatment.