Publications (2)3.17 Total impact
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Article: Analysis of gene expression profiles in rat hippocampus following treatment with nicotine and an alpha7 nAChR selective agonist.
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ABSTRACT: The nicotinic acetylcholine receptors (nAChRs) play critical roles in neuronal transmission and modulation. Among the diverse nAChRs, the alpha7 subtype has been considered as a potential therapeutic target for treating cognitive deficits associated with neuropsychiatric and neurodegenerative diseases. Although a number of mechanisms including neurotransmitter and biochemical effects linking alpha7 nAChR activation and cognitive function are beginning to be described, the underlying molecular processes especially following repeated administration remain unclear. To address this, we have performed gene expression analysis in rats treated with nicotine and a selective alpha7 nAChR agonist, PNU-282987. Our results showed significant overlap in gene expression changes induced by PNU-282987 and nicotine, suggesting convergent pathways triggered by these compounds. Treatment with nicotine also resulted in regulation of a number of genes that were not regulated by PNU-282987, consistent with the interaction of nicotine with other nAChRs beyond the alpha7 subtype. Interestingly, these gene expression changes were observed 24 h post-dose, suggesting that both nicotine and PNU-282987 cause protracted changes in gene expression. Overall, our results identify gene expression changes that may contribute to further defining the roles of nAChR activation in cognitive function.Neuroscience Research 04/2008; 60(3):266-74. · 2.25 Impact Factor -
Article: Development of an in vitro gene expression assay for predicting hepatotoxicity.
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ABSTRACT: A significant number of compounds do not proceed in drug discovery due to toxicity issues. The purpose of this study was to evaluate whether gene expression profiles could be identified and used to classify drugs based on the mechanism of toxicity in an in vitro system. Rat hepatocytes were treated with two classes of drugs, aromatic hydrocarbon receptor (AhR) and peroxisome proliferator activated receptor (PPAR) ligands. The results showed that a small set of genes could be identified that could be used to classify new compounds with distinct mechanisms of toxicity.ALTEX: Alternativen zu Tierexperimenten 02/2006; 23 Suppl:326-31. · 0.92 Impact Factor
