Korean J Psychopharmacol.  2007 Jul;18(4):211-220.

Common Gene Expression Pattern in the Rat Brain Induced by Several Mood: Stabilizing Drugs

Affiliations
  • 1Damyang Chamsarang Hospital, Jeonnam, Korea.
  • 2Department of Psychiatry & Research Institute of Medical Science, Chonnam National University Medical School, Gwangju, Korea. kys@snu.ac.kr
  • 3Department of Psychiatry and Behavioral Science, Institute of Human Behavioral Medicine, Korea.
  • 4Research Division of Human Life Science, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea.

Abstract


OBJECTIVE
This study sought to identify candidate genes related to the clinical effects of several mood stabilizers through gene expression profiles using microarrays and real time RT-PCR. METHOD: Rats were treated with lithium carbonate, valproate, or clozapine for 10 days. Total RNA was extracted from the rat brains and used for microarray analysis. Of 54 genes showing more than 1.5-fold changes induced by all three mood stabilizers, seven genes were selected, and drug-induced changes in gene expression were confirmed by real time RT-PCR. In addition, genotype distribution of the GRIK2 gene was compared between 181 patients with bipolar disorder and 350 normal controls.
RESULTS
Of the seven candidate genes, GRIK2 and PRKAR were confirmed as being downregulated by lithium and valproate. However, none of the genes was affected by all three drugs. The allele and genotype distribution in two SNPs of GRIK2 did not differ between the patient and control groups.
CONCLUSIONS
Although this study demonstrated overall negative results, the present findings will be used in future studies for establishing various mechanisms of mood stabilizers.

Keyword

Bipolar; Lithium; Valproate; Clozapine; Candidate gene; Microarray; RT-PCR; GRIK2; Polymorphism

MeSH Terms

Alleles
Animals
Bipolar Disorder
Brain*
Clozapine
Gene Expression*
Genotype
Humans
Lithium
Lithium Carbonate
Microarray Analysis
Polymorphism, Single Nucleotide
Rats*
RNA
Transcriptome
Valproic Acid
Clozapine
Lithium
Lithium Carbonate
RNA
Valproic Acid
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