NR AYGI
AU Xiang,W.; Hummel,M.; Mitteregger,G.; Pace,C.; Windl,O.; Mansmann,U.; Kretzschmar,H.A.
TI Transcriptome analysis reveals altered cholesterol metabolism during the neurodegeneration in mouse scrapie model
QU Journal of Neurochemistry 2007 Aug; 102(3): 834-47
PT journal article; research support, non-u.s. gov't
AB To identify the dynamic transcriptional alterations in CNS during the development of prion disease, brains of scrapie-infected 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 mock-inoculated 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 age-related genes and scrapie-associated neurodegeneration.
MH Aging/genetics; Animals; Brain/*metabolism/physiopathology; Cholesterol/*biosynthesis; Disease Models, Animal; Down-Regulation/genetics; Female; Gene Expression Profiling/methods; Gene Expression Regulation/*genetics; Mice; Mice, Inbred C57BL; Multigene Family/genetics; Nerve Degeneration/genetics/*metabolism/physiopathology; Oligonucleotide Array Sequence Analysis; RNA, Messenger/analysis/*genetics; Reverse Transcriptase Polymerase Chain Reaction; Scrapie/genetics/*metabolism/physiopathology; Trans-Activation (Genetics)/genetics
AD Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
SP englisch
PO England