Chronic thrombin exposure results in an increase in apolipoprotein-E levels.
Chronic thrombin exposure results in an increase in apolipoprotein-E levels.
复制标题
慢性凝血酶暴露会导致载脂蛋白-E 水平升高。
DOI：
10.1002/jnr.20887
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发表时间：
2006
影响因子：
4.2
通讯作者：
Grammas,Paula
中科院分区：
文献类型：
--
作者：
Mhatre,Molina;Hensley,Kenneth;Nguyen,Albert;Grammas,Paula
研究表明，有创伤性脑损伤史和遗传载脂蛋白E-4（ApoE4）等位基因的个体与神经功能不良和阿尔茨海默病风险增加有关。我们评估了脑损伤期间释放的凝血酶导致载脂蛋白-E水平升高的假设，载脂蛋白-E4亚型水平的升高可能具有淀粉样蛋白生成作用。大鼠通过脑室内（i.c.v.）输液凝血酶处理增加海马中的载脂蛋白E水平与载体处理相比（P <0.001）。输注人载脂蛋白-E4（0.6 ng/hr，i.c.v.，56天）导致β淀粉样蛋白沉积并增加GFAP阳性星形胶质细胞的数量。ApoE4输注也导致显著的空间记忆缺陷。这些发现表明，脑损伤期间释放的凝血酶可能有助于载脂蛋白E水平的增加。载脂蛋白E4亚型的这种增加促进β淀粉样蛋白沉积和认知缺陷。© 2006 Wiley利斯公司
Studies have shown that individuals with both a history of traumatic brain injury and inheritance of apolipoprotein E‐4 (ApoE4) allele are associated with a poor neurologic outcome and an increased risk for Alzheimer's disease. We assessed the hypothesis that thrombin released during brain injury causes an increase in apolipoprotein‐E levels and such increase in the levels of apolipoprotein‐E4 isoform may have amyloidogenic effects. Rats received either thrombin (100 nm, 0.25 μl/hr, 28 days) or vehicle via intracerebroventricular (i.c.v.) infusion. Thrombin treatment increased apolipoprotein‐E levels in hippocampus as compared to vehicle treatment (P< 0.001). Infusion of human apolipoprotein‐E4 (0.6 ng/hr, i.c.v., 56 days) into rats resulted in β‐amyloid deposition and increased the number of GFAP‐positive astrocytes. ApoE4 infusion also resulted in significant spatial memory deficits. These findings suggest that thrombin released during brain injury may contribute to an increase in apolipoprotein‐E levels. Such increase in Apolipoprotein‐E4 isoform facilitates β‐amyloid deposition and cognitive deficits. © 2006 Wiley‐Liss, Inc.