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Effects of Olanzapine on Gene Expression Changes in MK-801-induced Neurotoxicity Using a High-density DNA Microarray  

Jo, Jae-Hoon (College of Pharmacy, Chungnam National University)
Kim, Seung-Jun (Genocheck Co. Ltd.)
Yeon, Jong-Pil (Genocheck Co. Ltd.)
Oh, Moon-Ju (Genocheck Co. Ltd.)
Seo, Hye-Myung (Division of Molecular & Life Sciences, Hanyang University)
Hwang, Seung-Yong (Genocheck Co. Ltd.)
Kim, Sang-Kyum (College of Pharmacy, Chungnam National University)
Kim, Bong-Hee (College of Pharmacy, Chungnam National University)
Publication Information
Molecular & Cellular Toxicology / v.3, no.4, 2007 , pp. 282-291 More about this Journal
Abstract
Although the etiology of schizophrenia is known to be linked with the disturbance of glutamatergic and dopaminergic neurotransmission, little is known about the relationship between gene expression and the disease process. To identify genes related to abnormalities in glutamatergic and dopaminergic function, we investigated the effects of olanzapine in the changes of mRNA levels in the animal model of schizophrenia, using a high-density DNA microarray. Olanzapine (3.0 mg/kg, i.p.) significantly reduced hyperlocomotive activities, which was induced by MK-801 (1.0 mg/kg, i.p.). We identified that the expression of 719 genes were significantly altered more than two folds in the prefrontal cortex of the rats treated with MK-801. We selected 15 genes out of them by the changes of the expression pattern in the treatment of Olanzapine and/or MK801 for the further confirmation in RT-PCR. The administration of MK-801 increased the expression of 7 genes (NOS3, Hspb1, Hspa1a, CRH, Serpine1, Igfbp6, Snf1lk) and decreased the expression of 1 gene (Aldh1a2), which was attenuated by olanzapine. One gene (Prss12) was up-regulated after olanzapine treatment although it did not show the significant changes after MK-801 treatment. These results showed that antipsychotic drug, such as olanzapine, may alter the gene expression patterns, which were accompanied by MK-801-induced psychosis. Our results also provide us high-density DNA microarray technology could be potential approaches to find the candidate molecules for the therapeutics and also for the early diagnosis of psychiatric diseases.
Keywords
DNA microarray; Schizophrenia; Olanzapine; MK-801; Gene expression;
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Times Cited By Web Of Science : 2  (Related Records In Web of Science)
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