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Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Substantia Nigra.

Authors :
Miller, Renee M.
Callahan, Linda M.
Casaceli, Cindy
Chen, Linlin
Kiser, Gretchen L.
Chui, Buena
Kaysser-Kranich, Tamma M.
Sendera, Timothy J.
Palaniappan, Chockalingam
Federoff, Howard J.
Source :
Journal of Neuroscience. 8/25/2004, Vol. 24 Issue 34, p7445-7454. 10p. 4 Diagrams, 2 Charts, 2 Graphs.
Publication Year :
2004

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02706474
Volume :
24
Issue :
34
Database :
Academic Search Index
Journal :
Journal of Neuroscience
Publication Type :
Academic Journal
Accession number :
14563374
Full Text :
https://doi.org/10.1523/JNEUROSCI.4204-03.2004