Changes in iNOS, GFAP and NR1 expression in various brain regions and elevation of sphingosine-1-phosphate in serum after immobilized stress
Changes in iNOS, GFAP and NR1 expression in various brain regions and elevation of sphingosine-1-phosphate in serum after immobilized stress
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DOI：
10.1007/s11064-007-9523-6
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Oh, Seikwan
中科院分区：
文献类型：
--
作者：
Jang, Soyong;Suh, Suk Hyo;Oh, Seikwan
一些研究表明，长期暴露于压力对各种大脑功能有不利影响，并导致神经退行性变化。然而，压力引起脑损伤或神经退行性变化的确切机制仍然是一个争论的问题。本研究探讨了神经元细胞的损伤，参与表达的iNOS，NR 1，和GFAP在不同的大脑区域和特点的变化，鞘脂代谢物作为生物标志物的生理变化在血清中反复制动后3周。本研究观察了慢性束缚应激对大鼠脑内iNOS、GFAP和NR 1表达的影响。反复制动3周后，皮质和海马区iNOS、GFAP和NR 1的表达明显增加。胶质纤维酸性蛋白和波形蛋白的免疫反应性，作为反应性胶质增生的标志物，也在皮质和海马升高。测量鞘脂水平，以评估暴露于应激的大鼠血清中鞘脂代谢物的变化。有趣的是，血浆中的SO-1-P的水平增加，进行6小时的制动应力比重复制动。为了进一步研究不同脑区SO-1-P增加的调节作用，将SO-1-P以100 pmol/10 μ l/h的速率注入侧脑室7天。侧脑室注射SO-1-P后，皮质、海马、纹状体和小脑中iNOS和NR 1的表达增加，海马和纹状体中GFAP的表达增加。有趣的是，诱导型一氧化氮合酶，GFAP，和NR 1的表达水平增加，直接应用SO-1-P培养的皮质细胞。这些结果表明，NO的产生通过iNOS的表达，NR 1的表达，星形胶质细胞的激活，以及SO-1-P的升高可能导致慢性制动大鼠的神经退行性变化，SO-1-P的升高可能是应激暴露的应激信号分子之一。
Several studies have been suggested that long-term exposure to stress has detrimental effects on various brain functions and leads to neurodegenerative changes. However, the precise mechanism by which stress induces brain damage or neurodegenerative change is still a matter of debate. This study investigated the damage of neuronal cells involving in the expression of iNOS, NR1, and GFAP in various brain regions and characterized the change of sphingolipid metabolites as a biomarker of physiological change in serum after 3 weeks of repeated immobilization. In this report, the expression of iNOS, GFAP and NR1 in the brain of rats exposed to chronic immobilization stress was investigated. The expression of iNOS, GFAP and NR1 was elevated in the cortex and hippocampal area after 3 weeks of repeated immobilization. Immunoreactivity for GFAP and vimentin, as a marker of reactive gliosis, was also elevated in the cortex and hippocampus. The level of sphingolipids was measured in order to assess the changes in sphingolipid metabolites in the serum of rats exposed to stress. Interestingly, the level of So-1-P was increased in the plasma of rats subjected to 6-h immobilization stress than repeated immobilization. To further investigate the modulating effect of increased So-1-P in various brain regions, So-1-P was infused into the lateral cerebroventricle at a rate of 100 pmol/10 mu l/h for 7 days. The expression of iNOS and NR1 was elevated in the cortex, hippocampus, striatum, and cerebellum after So-1-P infusion into the cerebroventricle, while the level of GFAP was elevated in the hippocampus and striatum. Interestingly, the expression levels of iNOS, GFAP, and NR1 were increased by the direct application of So-1-P to cultured cortical cells. These results suggest that NO production via iNOS expression, the NR1 expression, the activation of astrocytes, and the elevation of So-1-P may cause neurodegenerative changes in rats subjected to chronic immobilization and that the elevation of So-1-P by stress exposure would be one of the stress signal molecules.