Analysis of expression regulation of selenoproteins in neurons and Gliazellen

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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.