.6-ohda Into The Damaged Rat Model Of Parkinson's Disease Striatum Differentially Expressed Gene Screening And Functional Studies

To identify adaptive response-associated genes in the dopamine denervatedstriatum, both suppressive subtractive hybridization and DNA microarray wereemployed in this study. Approximately 18 differentially expressed genes wereidentified in the denervated rat striatum. Their expression pattern were verified ateither RNA or protein level. Among these genes, cystatin C, trophinin and bystin wereselected for further studies.Cystatin C is a type II cystine protease inhibitor. Northern blot analysis and insitu hybridization showed that its mRNA level was up-regulated in the DA-denervatedstritum.The differential expression of cystatin C was verified in immunohistochemicalanalysis. The double-labeled immunohistochemistry showed that part of astrocytesand microglia were cystatin C positive cells in the striatum. Moreover, treatment offetal mesencephalic cultures with cystatin C delayed DA cells death in adose-dependent manner compared to the sham controls. Administration of cystatin Calso partially protected nigral dopamine neurons in vivo. These results suggest thatcystatin C may be involved in pathogenesis of 6-hydroxydopamine-inducedneurotoxicity as well as protection of DA neurons.Trophinin and bystin are known to be important adhension molecules in embryoimplantation. However, the presence and the roles of these twomolecules in the CNShave not been studied.Their altered expression patterns in the substantia nigra and thestriatum in the rat parkinson model suggest that they may be involved in the processof neurodegeneration or regeneration.