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KMID : 0361520070180040211
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Korean Journal of Psychopharmacology
2007 Volume.18 No. 4 p.211 ~ p.220
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Common Gene Expression Pattern in the Rat Brain Induced by Several Mood-Stabilizing Drugs
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Bae Seung-Oh
Kim Jae-Min
Ahn Yong-Min
Lee Kyu-Young
Roh Jae-Woo
Yoon Jin-Sang
Kim Yong-Sik
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Abstract
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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 down-regulated 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.
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KEYWORD
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Bipolar, Lithium, Valproate, Clozapine, Candidate gene, Microarray, RT-PCR, GRIK2, Polymorphism
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