Identification of upregulated genes in scrapie-infected brain tissue

The pathogenesis of scrapie, and of neurodegenerative diseases in general, is still insufficiently understood and is therefore being intensely researc hed. There is abundant evidence that the activation of glial cells precedes neurodegeneration and may thus play an important role in disease developme nt and progression. The identification of genes with altered expression pat terns in the diseased brain may provide insight on the molecular level into the process which ultimately leads to neuronal loss. Differentially expres sed genes in scrapie-infected brain tissue were enriched by the suppression subtractive hybridization technique, molecularly cloned, and further chara cterized. Northern blotting and nucleotide sequencing confirmed the identit ies of 19 upregulated genes, 11 of which were unknown to be affected by scr apie. A considerable number of these 19 genes, namely those encoding interf eron-inducible protein 10 (IP-10), 2',5'-oligo(A) synthetase, Mx protein, I IGP protein, major histocompatibility complex classes I and II, complement, and beta(2)-microglobulin, were inducible by interferons (IFNs), suggestin g that an IFN response is a possible mechanism of gene activation in scrapi e. Among the newly found genes, that coding for 2',5'-oligo(A) synthetase i s of special interest because it could contribute to the apoptotic loss of neuronal cells via RNase L activation. In addition, upregulation of the che mokine IP-10 and B-lymphocyte chemoattractant mRNAs was seen at relatively early stages of the disease and was sustained throughout disease developmen t.