Effect of mood stabilizers on gene expression in lymphoblastoid cells.
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 microg 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.
Sugawara
Hiroko
H
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Iwamoto
Kazuya
K
Bundo
Miki
M
Ishiwata
Mizuho
M
Ueda
Junko
J
Kakiuchi
Chihiro
C
Ishigooka
Jun
J
Kato
Tadafumi
T
D000328:Adult; D018692:Antimanic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014635:Valproic Acid / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D018692:Antimanic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014635:Valproic Acid; D008094:Lithium