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Effect of mood stabilizers on gene expression in lymphoblastoid cells

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Lithium and valproate are widely used as effective mood stabilizers for the treatment of bipolar disorder. To elucidate the common molecular effect of these drugs on non-neuronal cells, we studied the gene expression changes induced by these drugs. Lymphoblastoid cell cultures derived from lymphocytes harvested from three healthy subjects were incubated in medium containing therapeutic concentrations of lithium (0.75 mM) or valproate (100 μg ml−1) for 7 days. Gene expression profiling was performed using an Affymetrix HGU95Av2 array containing approximately 12,000 probe sets. We identified 44 and 416 genes that were regulated by lithium and valproate, respectively. Most of the genes were not commonly affected by the two drugs. Among the 18 genes commonly altered by both drugs, vascular endothelial growth factor A (VEGFA), which is one of the VEGF gene isoforms, showed the largest downregulation. Our findings indicate that these two structurally dissimilar mood stabilizers, lithium, and valproate, alter VEGFA expression. VEGFA might be a useful biomarker of their effects on peripheral tissue.

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Acknowledgments

We are grateful to the Research Resource Center of our institute for performing the microarray analysis. This work was supported in part by a Grant-in-Aid from the Japanese Ministry of Health and Labor; Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science, and Technology; and Grants-in-Aid for Mental Health Research from Ministry of Health, Labor, and Welfare.

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Authors and Affiliations

  1. Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Hiroko Sugawara, Kazuya Iwamoto, Miki Bundo, Mizuho Ishiwata, Junko Ueda & Tadafumi Kato

  2. Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan

    Hiroko Sugawara & Jun Ishigooka

  3. Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Chihiro Kakiuchi

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  1. Hiroko Sugawara
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  2. Kazuya Iwamoto
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  4. Mizuho Ishiwata
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  8. Tadafumi Kato
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Correspondence to Tadafumi Kato.

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Sugawara, H., Iwamoto, K., Bundo, M. et al. Effect of mood stabilizers on gene expression in lymphoblastoid cells. J Neural Transm 117, 155–164 (2010). https://doi.org/10.1007/s00702-009-0340-8

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