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Series GSE4788 Query DataSets for GSE4788
Status Public on May 12, 2006
Title Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioined Mouse Substantia Nigra
Organism Mus musculus
Experiment type Expression profiling by array
Summary Parkinson's disease pathogenesis proceeds through several phases, culminating in the loss of dopaminergic neurons of the substantia nigra (SN). Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of oxidative SN injury is frequently used to study degeneration of dopaminergic neurons in mice and non-human primates, an understanding of the temporal sequence of molecular events from inhibition of mitochondrial complex 1 to neuronal cell death is limited. Here, microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration. This approach enabled the identification of small, yet consistently significant, changes in gene expression within the SN of MPTP-treated animals. Such an analysis disclosed dysregulation of genes in three main areas related to neuronal function: cytoskeletal stability and maintenance, synaptic integrity, and cell cycle and apoptosis. The discovery and validation of these alterations provide molecular evidence for an evolving cascade of injury, dysfunction, and cell death.
Keywords: Parkinson's disease; MPTP; gene expression; microarray; cytoskeleton; mouse
Overall design The demonstration of a shared pathogenic cascade among the differently triggered forms of PD requires a characterization of the molecular changes accompanying the temporal evolution of midbrain dopamine injury, dysfunction, and cell death. Identification of consensus molecular responses is aided by the application of robust exploratory methods that permit cataloging of changes in gene expression. Here, mRNA profiling by two leading oligonucleotide array systems, Affymetrix GeneChips and Amersham CodeLink, was used to reveal candidate molecules that are dysregulated during MPP+-induced injury of the mouse SN in a chronic MPTP model of PD. Different time points were examined to discriminate temporal patterns of gene expression in this model. Applying three separate data mining methods, we found consistent downregulation of genes encoding proteins functioning in the maintenance of the cytoskeleton, neurotransmitter release, and trophic signaling in the SN. Additionally, decline in cell cycle regulatory genes is suggestive of abortive mitosis and death of postmitotic neurons.
Contributor(s) Miller RM, Callahan LM, Casaceli C, Chen L, Kiser GL, Chui B, Kaysser-Kranich TM, Sendera TJ, Palaniappan C, Federoff HJ
Citation(s) 15329391
Submission date May 08, 2006
Last update date Jul 06, 2016
Contact name Howard J Federoff
Phone (585) 273-2190
Organization name University of Rochester
Department Center for Aging and Developmental Biology
Lab Federoff
Street address 601 Elmwood Ave Box 645
City Rochester
State/province NY
ZIP/Postal code 14642
Country USA
Platforms (2)
GPL32 [MG_U74A] Affymetrix Murine Genome U74A Array
GPL2892 GE Healthcare/Amersham Biosciences CodeLinkā„¢ UniSet Mouse I Bioarray
Samples (23)
GSM107845 Substantia Nigra Control Sample1 RMA, MAS 5, dChip
GSM108079 Substantia Nigra Control Sample2 RMA, MAS 5, dChip
GSM108080 Substantia Nigra Control Sample3 RMA, MAS 5, dChip
BioProject PRJNA95725

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE4788_RAW.tar 41.2 Mb (http)(custom) TAR (of CEL)

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