1. Effects of lithium chloride on the gene expression profiles in Drosophila heads.
- Author
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Kasuya J, Kaas G, and Kitamoto T
- Subjects
- Amino Acids metabolism, Animals, Antimanic Agents pharmacology, Drosophila Proteins biosynthesis, Drosophila Proteins drug effects, Drosophila Proteins genetics, Drosophila melanogaster anatomy & histology, Gene Expression Profiling methods, Nerve Tissue Proteins biosynthesis, Nerve Tissue Proteins drug effects, Nerve Tissue Proteins genetics, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Brain drug effects, Brain metabolism, Drosophila melanogaster drug effects, Drosophila melanogaster genetics, Gene Expression Regulation drug effects, Lithium Chloride pharmacology
- Abstract
To gain insight into the basic neurobiological processes regulated by lithium--an effective drug for bipolar disorder--we used Affymetrix Genome Arrays to examine lithium-induced changes in genome-wide gene expression profiles of head mRNA from the genetic model organism Drosophila melanogaster. First, to identify the individual genes whose transcript levels are most significantly altered by lithium, we analyzed the microarray data with stringent criteria (fold change>2; p<0.001) and evaluated the results by RT-PCR. This analysis identified 12 genes that encode proteins with various biological functions, including an enzyme responsible for amino acid metabolism and a putative amino acid transporter. Second, to uncover the biological pathways involved in lithium's action in the nervous system, we used less stringent criteria (fold change>1.2; FDR<0.05) and assigned the identified 66 lithium-responsive genes to biological pathways using DAVID (Database for Annotation, Visualization and Integrated Discovery). The gene ontology categories most significantly affected by lithium were amino acid metabolic processes. Taken together, these data suggest that amino acid metabolism is important for lithium's actions in the nervous system, and lay a foundation for future functional studies of lithium-responsive neurobiological processes using the versatile molecular and genetic tools that are available in Drosophila.
- Published
- 2009
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