A microarray gene expression study of the molecular pharmacology of lithium carbonate on mouse brain mRNA to understand the neurobiology of mood stabilization and treatment of bipolar affective disorder - UCL EprintsObjectives: Lithium is the most widely prescribed and effective mood-stabilizing drug used for the treatment of bipolar affective disorder. To understand how lithium produces changes in the brain, we studied brain mRNA from10 mice after treatment with lithium and compared them with 10 untreated controls. Methods: We used the MAS 5.0, Smudge miner, GC-RMA and FDR-AME packages of software to determine gene expression changes using Affymetrix MOE430E 2.0 microarrays after 2 weeks of lithium treatment. Results: We used both a false discovery rate (FDR-AME) assessment of significance and the Bonferroni method to correct for the possibility of false-positive changes in gene expression among the 39 000 genes present in each array. Our primary method of analysis was to use t-tests on normalized gene expression intensities. By using a Bonferroni correction of P 1.28 10–6, we found that 121 genes showed significant changes in expression. The three genes with the most changed mRNA expression were alanine-glyoxylate aminotransferase 2-like 1 (Agxt2l1), cmer proto-oncogene tyrosine kinase (Mertk) and sulfotransferase family 1A phenol-preferring member 1 (Sult1a1). Also among the group of 121 genes with significant changes in gene expression that survived Bonferroni correction (Table 2) were the genes encoding the Per2 period gene (Per2 P =1.33x10–8, 2.47-fold change), the metabotropic glutamate receptor (Grm3, P = 9.48x10–7, 0.7-fold change) and secretogranin II (Scg2, P = 9.48x10–7, 1.28-fold change) as well several myelinrelated genes and protein phosphatases. By taking a significance value of P 0.05 without Bonferroni or FDRAME correction, we identified a total of 4474 genes showing changed mRNA expression in response to lithium.
