Transcriptome analysis reveals altered cholesterol metabolism during the neurodegeneration in mouse scrapie model.
J Neurochem
; 102(3): 834-47, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17437544
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Scrapie
/
Encéfalo
/
RNA Mensageiro
/
Regulação da Expressão Gênica
/
Colesterol
/
Degeneração Neural
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha