| | |  | | | | Record from Web of Science® | | | | | | |
| Chronic olanzapine treatment causes differential expression of genes in frontal cortex of rats as revealed by DNA microarray technique |
|
|
| Author(s): Fatemi SH (Fatemi, S. Hossein), Reutiman TJ (Reutiman, Teri J.), Folsom TD (Folsom, Timothy D.), Bell C (Bell, Christopher), Nos L (Nos, Lisa), Fried P (Fried, Peter), Pearce DA (Pearce, David A.), Singh S (Singh, Sushmita), Siderovski DP (Siderovski, David P.), Willard FS (Willard, Francis S.), Fukuda M (Fukuda, Mitsunori) |
| Source: NEUROPSYCHOPHARMACOLOGY Volume: 31 Issue: 9 Pages: 1888-1899 Published: SEP 2006 |
| Times Cited: 31 References: 65 |
| Abstract: Recent emerging biochemical data indicate that several important neuroregulatory genes and proteins may be involved in the etiology of schizophrenia and bipolar disorder. Additionally, the same genes appear to be targets of several psychotropic medications that are used to treat these disorders. Recent DNA microarray studies show that genes involved in synaptic neurotransmission, signal transduction, and glutamate/GABA regulation may be differentially regulated in brains of subjects with schizophrenia. We hypothesized that chronic administration of olanzapine to rats would alter expression of various genes that may be involved in the etiology of schizophrenia and mood disorders. Rats were administered olanzapine (N = 20, 2 mg/kg/day) or sterile saline intraperitoneally (N = 20) daily for 21 days. Control and olanzapine-treated frontal cortices were analyzed using cDNA microarray technology. The results showed significant downregulation of 31 genes and upregulation of 38 genes by greater than two-fold in the drug-treated brains vs controls. Our results provide evidence for altered regulation of genes involved with signal transduction and cell communication, metabolism and energy pathways, transport, immune response, nucleic acid metabolism, and neuronal growth factors. Real-time quantitative RT-PCR analysis verified the direction and magnitude of change in six genes of interest: calbindin 3, homer 1, regulator of G-protein signaling (RGS) 2, pyruvate kinase, Reelin and insulin 2. Western blotting showed significant upregulation in protein products for Reelin 410 and Reelin 180 kDa and downregulation for NMDA3B and RGS2. Our results show for the first time that olanzapine causes changes in levels of several important genes that may be involved in the etiology and treatment of schizophrenia and other psychiatric disorders. |
| Document Type: Proceedings Paper |
| Language: English |
| Reprint Address: Fatemi, SH (reprint author), Univ Minnesota, Sch Med, Div Neurosci Res, Dept Psychiat, MMC 392,420 Delaware St SE, Minneapolis, MN 55455 USA |
Addresses:
1. Univ Minnesota, Sch Med, Div Neurosci Res, Dept Psychiat, Minneapolis, MN 55455 USA
2. Univ Rochester, Sch Med, Ctr Funct Genomics, Dept Biochem & Biophys, Rochester, NY USA
3. Univ Minnesota, Biomed Genomics Ctr, Minneapolis, MN USA
4. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA
5. RIKEN, Fukuda Initiative Res Unit, Wako, Saitama 35101 Japan |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Neurosciences; Pharmacology & Pharmacy; Psychiatry |
| IDS Number: 075XJ |
| ISSN: 0893-133X |
| DOI: 10.1038/sj.npp.1301002 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |