Journal
JOURNAL OF NEUROCHEMISTRY
Volume 102, Issue 3, Pages 834-847Publisher
WILEY
DOI: 10.1111/j.1471-4159.2007.04566.x
Keywords
age-related gene; cholesterol metabolism; microarray; neurodegeneration; prion disease; scrapie
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To identify the dynamic transcriptional alterations in CNS during the development of prion disease, brains of scrapieinfected mice and age-matched, mock-inoculated controls were analyzed immediately before inoculation and at different time points post-inoculation using Affymetrix microarray technique. A total of 449 probe sets, representing 430 genes, showed differential expression between scrapie- and mockinoculated mice over the time course. These genes could be separated into two clusters according to expression patterns: the genes in cluster 1 demonstrated lower mRNA levels in scrapie-infected brains when compared with mock-inoculated brains, whereas genes in cluster 2 showed higher mRNA levels in scrapie-infected brains. Functional analysis of differentially expressed genes revealed the most severely affected biological process: cholesterol metabolism. The expression patterns of the cholesterol-related genes indicated an inhibited cholesterol synthesis in the diseased brains. Conspicuously, a number of cluster 1 genes, including some of cholesterol-related genes, showed not only decreasing mRNA levels in scrapie-infected brains but also increasing mRNA levels in mock-inoculated brains with increasing age. Quantitative RT-PCR analysis of some cholesterol-related genes in untreated mice suggested that changes of the examined genes observed in mock-inoculated brains are mainly age related. This finding indicated a link between agerelated genes and scrapie-associated neurodegeneration.
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