Sequential and concerted gene expression changes in a chronic in vitro model of parkinsonism

• Type of Material: Article
• Authors: James G Greene, Emory University; J. Timothy Greenamyre, University of Pittsburgh; Raymond J Dingledine, Emory University
• Language: English
• Date: 2008-03-03
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neuroscience.2007.11.029
• Title of Journal or Parent Work: Neuroscience
• ISSN: 0306-4522
• Volume: 152
• Issue: 1
• Start Page: 198
• End Page: 207
• Grant/Funding Information: Supported by NINDS NS048858 (JGG), NIEHS ES012068 (JTG), the Picower Foundation (JTG), and a Cotzias Fellowship from the American Parkinson Disease Association (JGG).
• Keywords: microarray; neurodegeneration; oxidative stress; rotenone; mitochondria; Parkinson’s disease
• Research Categories: Biology, Neuroscience

Abstract

Many mechanisms of neurodegeneration have been implicated in Parkinson’s disease, but which ones are most important and potential interactions among them are unclear. To provide a broader perspective on the parkinsonian neurodegenerative process, we have performed a global analysis of gene expression changes caused by chronic, low-level exposure of neuroblastoma cells to the mitochondrial complex I inhibitor and parkinsonian neurotoxin rotenone. Undifferentiated SK-N-MC neuroblastoma cells were grown in the presence of rotenone (5 nM), and RNA was extracted at three different time points (baseline, 1 week, and 4 weeks) for labeling and hybridization to Affymetrix Human U133 Plus 2.0 GeneChips. Our results show that rotenone induces concerted alterations in gene expression that change over time. Particularly, alterations in transcripts related to DNA damage, energy metabolism, and protein metabolism are prominent during chronic complex I inhibition. These data suggest that early augmentation of capacity for energy production in response to mitochondrial inhibition might be deleterious to cellular function and survival. These experiments provide the first transcriptional analysis of a rotenone model of Parkinson’s disease and insight into which mechanisms of neurodegeneration may be targeted for therapeutic intervention.