Korean J Psychopharmacol.  2003 Dec;14(4):360-366.

Search of Altered Gene Expression after Chronic Administration of Olanzapine in the Rat Frontal Cortex using cDNA Microarray

Affiliations
  • 1Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Korea.
  • 2Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
  • 3Human Genome Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 4Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea.

Abstract


OBJECTIVE
cDNA microarray is a convenient molecular technology that enables to search for gene expression in large scale. To explore the effect of antipsychotics on the gene expression in the brain, we applied cDNA microarray and searched for differentially expressed genes in the olanzapine-treated rat frontal cortex. METHODS: We administered olanzapine (4 mg/kg/day, IP) to S-D rats for 14days, and dissected the frontal cortex to examine. We analyzed altered gene expression from microarray, and screened up- or down-regulated genes. Their changes were confirmed by RT-PCR. RESULTS: Three down-regulated and one up-regulated genes were screened by triplicate cDNA microarray analysis. Among them, translocase of the inner mitochondrial membrane 23 (TIM23) was confirmed in RT-PCR. The expression of TIM23 mRNA was significantly increased in olanzapine-treated rat frontal cortex. CONCLUSION: This is the first report of up-regulated gene expression of TIM23 by antipsychotics in the rat brain. TIM23 is the essential component of mitochondrial biogenesis. From this result, we suggest that antipsychotic effect may be related to the improvement of mitochondrial dysfunction in the brain.

Keyword

Olanzapine; Antipsychotics; Gene expression; DNA microarray; TIM23; Schizophrenia

MeSH Terms

Animals
Antipsychotic Agents
Brain
DNA, Complementary*
Gene Expression*
Mitochondrial Membranes
Organelle Biogenesis
Oligonucleotide Array Sequence Analysis*
Rats*
RNA, Messenger
Schizophrenia
Antipsychotic Agents
DNA, Complementary
RNA, Messenger
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