Analysis of expression regulation of selenoproteins in neurons and Gliazellen

自由基和氧化应激诱导的神经元细胞死亡已被证明在各种神经系统疾病如缺血或阿尔茨海默病中起重要作用。因此，神经保护机制的研究是基础和临床神经科学的主要兴趣。硒蛋白W（Se-W）除了在几种动物的肌肉组织中有强表达外，在大鼠中枢神经系统中也有表达。原位杂交结果表明，该基因转录活性最高的部位位于海马角区。以前的研究结果表明，硒-W与谷胱甘肽（GSH），这表明这种蛋白质在氧化/还原催化的可能作用，从而使其成为一个神经保护因子的候选人。我们的目的是调查-通过原位杂交和免疫组织化学-Se-W在大鼠脑细胞水平上的解剖分布。将进行Se-W表达与细胞类型特异性免疫标记的进一步共定位，以鉴定表达该基因的CNS细胞的亚型。在神经元和小胶质细胞系中过表达克隆的Se-W cDNA，以分析该基因产物对氧化应激的可能保护特性。

Free radicals and oxidative stress-induced neuronal cell death has been shown to play an important role in a variety of neurological disorders such as ischemia or Alzheimer's disease. For this reason, the study of neuroprotective mechanisms is of primary interest in basic and clinical neuroscience. Beside its strong expression in muscle tissue of several species, Selenoprotein W (Se-W) is also expressed in the rat CNS. By in situ hybridization we could show that the highest transcriptional activity of this gene is located to the hippocampal cornu ammonis. Previous findings that Se-W is associated with glutathione (GSH) suggest a possible role for this protein in oxidation/reduction catalysis and thus make it a candidate for a neuroprotective facotr. Our aim is to investigate - by in situ hybridization and immunohistochemistry - the anatomical distribution of Se-W on a cellular level in the rat brain. Further colocalization of Se-W expression with cell-type specific immunological markers will be performed to identify the subtypes of CNS cells expressing the gene. Overexpression of the cloned Se-W cDNA in neuronal and microglial cell-lines is performed to analyze the possible protective properties of the gene product against oxidativ stress.