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sgk1, a member of an RNA cluster associated with cell death in a model of Parkinson's disease
- Source :
- The European journal of neuroscience. 21(2)
- Publication Year :
- 2005
-
Abstract
- In an effort to gain deeper insight into the molecular processes underlying neurodegeneration in Parkinson's disease, we performed gene expression profiling at several early time points after MPTP-injection into old (1-year) mice. We used a PCR-based gene expression profiling method, digital expression pattern display (DEPD), a method of very high sensitivity and reproducibility, which displays almost all transcripts of a tissue. To identify cell death-associated genes, we defined clusters of differentially expressed transcripts with expression behaviour that correlated with the temporal profile of cell death progression and characterized one of these cell death clusters further. We selected one of the strongest regulated genes, the serum and glucocorticoid-regulated kinase 1 (sgk1), and validated its differential expression by Northern blot analysis, semiquantitative PCR and in situ hybridization. Up-regulation of sgk1 (i) coincides with the onset of dopaminergic cell death in both the 8-week acute and 1-year subacute MPTP models, (ii) spans the entire brain, (iii) is attenuated by the l-deprenyl-mediated inhibition of the MPTP conversion to its active metabolite MPP+ and (iv) is not induced by dehydration. This study demonstrated that the combination of the DEPD technology, clustering analysis and a detailed histopathology is a useful tool for elucidating molecular pathways in neurodegenerative diseases.
- Subjects :
- Time Factors
Tyrosine 3-Monooxygenase
Gene Expression
In situ hybridization
Biology
Protein Serine-Threonine Kinases
Immediate early protein
Immediate-Early Proteins
Antiparkinson Agents
chemistry.chemical_compound
Mice
Parkinsonian Disorders
Gene expression
Glial Fibrillary Acidic Protein
Selegiline
medicine
Animals
Cluster Analysis
Drug Interactions
Northern blot
RNA, Messenger
In Situ Hybridization
Neurons
Cell Death
Water Deprivation
Reverse Transcriptase Polymerase Chain Reaction
General Neuroscience
MPTP
Gene Expression Profiling
Neurodegeneration
Age Factors
Brain
Nuclear Proteins
medicine.disease
Blotting, Northern
Molecular biology
Gene expression profiling
Blot
Disease Models, Animal
chemistry
Gene Expression Regulation
Astrocytes
Food Deprivation
Subjects
Details
- ISSN :
- 0953816X
- Volume :
- 21
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The European journal of neuroscience
- Accession number :
- edsair.doi.dedup.....7706390a063ecfd6f396d05ec036473d