Differential gene expression of scopolamine-treated rat hippocampus-application of cDNA microarray technology

The molecular study of learning and memory has been concentrated at muscarinic acetylcholine receptors and their associating signaling molecules. To explore alternative pathways we applied human cDNA microarray and searched for differentially expressed genes in the hippocampus of scopolamine-treated rat. Interspecies hybridization using human cDNA microarray to analyze scopolamine-treated rat hippocampus exhibited a minor difference for the expression profile compared to normal control with standard deviation of 0.08-fold in ratio. Based on differential expression, forty-two genes were selected for further analysis from 9,600 candidate genes on the array. Twenty-eight genes were validated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) using primer pairs against rat orthologs. The broad spectrum of the differentially expressed genes indicated an overall cellular response upon scopolamine treatment. In addition to genes associated with muscarinic receptor signaling pathways, we have disclosed genes associated with novel pathways such as apoptosis, cytoskeleton reconstruction, protein trafficking, cell differentiation, and genes without a clear role. Our result should provide an insight into the molecular study of scopolamine-induced memory impairment. (C) 2003 Elsevier Science Inc. All rights reserved.