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Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus

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Summary.

Altered expression of Disrupted-In-Schizophrenia-1 (DISC1) and dysbindin (DTNBP1), susceptibility genes for schizophrenia, in schizophrenic brain has been reported; however, the possible effect of antipsychotics on the expression levels of these genes has not yet been studied. We measured the mRNA expression levels of these genes in frontal cortex and hippocampus of mice chronically treated with typical and atypical antipsychotics by a real-time quantitative RT-PCR method. We found that atypical antipsychotics, olanzapine and risperidone, in a clinically relevant dose increased DISC1 expression levels in frontal cortex, while a typical antipsychotic, haloperidol, did not. No significant effect on dysbindin expression levels was observed in either brain region. These data suggest that prior evidence of decreased expression of dysbindin in postmortem brain of schizophrenics is not likely to be a simple artifact of antemortem drug treatment. Our results also suggest a potential role of DISC1 in the therapeutic mechanisms of certain atypical antipsychotics.

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References

  • MA Benson SE Newey E Martin-Rendon R Hawkes DJ Blake (2001) ArticleTitleDysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain J Biol Chem 276 24232–24241 Occurrence Handle11316798 Occurrence Handle1:CAS:528:DC%2BD3MXltVWisbg%3D Occurrence Handle10.1074/jbc.M010418200

    Article  PubMed  CAS  Google Scholar 

  • JH Callicott RE Straub L Pezawas MF Egan VS Mattay AR Hariri BA Verchinski A Meyer-Lindenberg R Balkissoon B Kolachana TE Goldberg DR Weinberger (2005) ArticleTitleVariation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia Proc Natl Acad Sci USA 102 8627–8632 Occurrence Handle15939883 Occurrence Handle1:CAS:528:DC%2BD2MXlsFCgt7o%3D Occurrence Handle10.1073/pnas.0500515102

    Article  PubMed  CAS  Google Scholar 

  • J Ekelund W Hennah T Hiekkalinna A Parker J Meyer J Lonnqvist L Peltonen (2004) ArticleTitleReplication of 1q42 linkage in Finnish schizophrenia pedigrees Mol Psychiatry 9 1037–1041 Occurrence Handle15197400 Occurrence Handle1:CAS:528:DC%2BD2cXovVGit70%3D Occurrence Handle10.1038/sj.mp.4001536

    Article  PubMed  CAS  Google Scholar 

  • J Ekelund I Hovatta A Parker T Paunio T Varilo R Martin J Suhonen P Ellonen G Chan JS Sinsheimer E Sobel H Juvonen R Arajarvi T Partonen J Suvisaari J Lonnqvist J Meyer L Peltonen (2001) ArticleTitleChromosome 1 loci in Finnish schizophrenia families Hum Mol Genet 10 1611–1617 Occurrence Handle11468279 Occurrence Handle1:CAS:528:DC%2BD3MXlvFOiurw%3D Occurrence Handle10.1093/hmg/10.15.1611

    Article  PubMed  CAS  Google Scholar 

  • B Funke CT Finn AM Plocik S Lake P DeRosse JM Kane R Kucherlapati AK Malhotra (2004) ArticleTitleAssociation of the DTNBP1 locus with schizophrenia in a U.S. population Am J Hum Genet 75 891–898 Occurrence Handle15362017 Occurrence Handle1:CAS:528:DC%2BD2cXptVSnsLs%3D Occurrence Handle10.1086/425279

    Article  PubMed  CAS  Google Scholar 

  • PJ Harrison DR Weinberger (2005) ArticleTitleSchizophrenia genes, gene expression, and neuropathology: on the matter of their convergence Mol Psychiatry 10 40–68 Occurrence Handle15263907 Occurrence Handle1:CAS:528:DC%2BD2cXhtFeisL3N Occurrence Handle10.1038/sj.mp.4001558

    Article  PubMed  CAS  Google Scholar 

  • R Hashimoto RE Straub CS Weickert TM Hyde JE Kleinman DR Weinberger (2004) ArticleTitleExpression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia Mol Psychiatry 9 299–307 Occurrence Handle14569272 Occurrence Handle1:CAS:528:DC%2BD2cXhvFCmsb8%3D Occurrence Handle10.1038/sj.mp.4001434

    Article  PubMed  CAS  Google Scholar 

  • W Hennah T Varilo M Kestila T Paunio R Arajarvi J Haukka A Parker R Martin S Levitzky T Partonen J Meyer J Lonnqvist L Peltonen J Ekelund (2003) ArticleTitleHaplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects Hum Mol Genet 12 3151–3159 Occurrence Handle14532331 Occurrence Handle1:CAS:528:DC%2BD3sXptVSntLw%3D Occurrence Handle10.1093/hmg/ddg341

    Article  PubMed  CAS  Google Scholar 

  • CA Hodgkinson D Goldman J Jaeger S Persaud JM Kane RH Lipsky AK Malhotra (2004) ArticleTitleDisrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder Am J Hum Genet 75 862–872 Occurrence Handle15386212 Occurrence Handle1:CAS:528:DC%2BD2cXptVSnsL8%3D Occurrence Handle10.1086/425586

    Article  PubMed  CAS  Google Scholar 

  • James R, Christie S, Buchanan SR, Porteous DJ, Millar JK (2004) Investigation of the cellular function of DISC1, a susceptibility gene for psychiatric illness. Program No 3476 2004 Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, DC

  • S Kapur ML Wadenberg G Remington (2000) ArticleTitleAre animal studies of antipsychotics appropriately dosed? Lessons from the bedside to the bench Can J Psychiatry 45 241–246 Occurrence Handle10779880 Occurrence Handle1:STN:280:DC%2BD3c3kt1WmsA%3D%3D

    PubMed  CAS  Google Scholar 

  • G Kirov D Ivanov NM Williams A Preece I Nikolov R Milev S Koleva A Dimitrova D Toncheva MC O’Donovan MJ Owen (2004) ArticleTitleStrong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria Biol Psychiatry 55 971–975 Occurrence Handle15121479 Occurrence Handle1:CAS:528:DC%2BD2cXjs1Gisrs%3D Occurrence Handle10.1016/j.biopsych.2004.01.025

    Article  PubMed  CAS  Google Scholar 

  • W Li Q Zhang N Oiso EK Novak R Gautam EP O’Brien CL Tinsley DJ Blake RA Spritz NG Copeland NA Jenkins D Amato BA Roe M Starcevic EC Dell’Angelica RW Elliott V Mishra SF Kingsmore RE Paylor RT Swank (2003) ArticleTitleHermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) Nat Genet 35 84–89 Occurrence Handle12923531 Occurrence Handle1:CAS:528:DC%2BD3sXmslemu7c%3D Occurrence Handle10.1038/ng1229

    Article  PubMed  CAS  Google Scholar 

  • BK Lipska ZZ Khaing CS Weickert DR Weinberger (2001) ArticleTitleBDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs Eur J Neurosci 14 135–144 Occurrence Handle11488957 Occurrence Handle1:STN:280:DC%2BD3MvktlGjsA%3D%3D Occurrence Handle10.1046/j.1460-9568.2001.01633.x

    Article  PubMed  CAS  Google Scholar 

  • Lipska BK, Horowitz C, Peters T, Weickert CS, Hyde TM, Egan MF, Callicott JH, Straub RE, Kleinman JE, Weinberger DR (2004) Expression of DISC1 in schizophrenia. Program No 1098 2004 Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, DC

  • McClintock W, Shannon Weickert C, Halim ND, Lipska BK, Hyde TM, Herman MM, Weinberger DR, Kleinman JE, Straub RE (2003) Reduced expression of dysbindin protein in the dorsolateral prefrontal cortex of patients with schizophrenia. Program No 3179 2003 Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, DC

  • JK Millar S Christie DJ Porteous (2003) ArticleTitleYeast two-hybrid screens implicate DISC1 in brain development and function Biochem Biophys Res Commun 311 1019–1025 Occurrence Handle14623284 Occurrence Handle1:CAS:528:DC%2BD3sXovVeisbc%3D Occurrence Handle10.1016/j.bbrc.2003.10.101

    Article  PubMed  CAS  Google Scholar 

  • JK Millar JC Wilson-Annan S Anderson S Christie MS Taylor CA Semple RS Devon DM Clair WJ Muir DH Blackwood DJ Porteous (2000) ArticleTitleDisruption of two novel genes by a translocation co-segregating with schizophrenia Hum Mol Genet 9 1415–1423 Occurrence Handle10814723 Occurrence Handle1:CAS:528:DC%2BD3cXjvFymsrc%3D Occurrence Handle10.1093/hmg/9.9.1415

    Article  PubMed  CAS  Google Scholar 

  • K Miyoshi A Honda K Baba M Taniguchi K Oono T Fujita S Kuroda T Katayama M Tohyama (2003) ArticleTitleDisrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth Mol Psychiatry 8 685–694 Occurrence Handle12874605 Occurrence Handle1:CAS:528:DC%2BD3sXlsFygur8%3D Occurrence Handle10.1038/sj.mp.4001352

    Article  PubMed  CAS  Google Scholar 

  • DW Morris KA McGhee S Schwaiger P Scully J Quinn D Meagher JL Waddington M Gill AP Corvin (2003a) ArticleTitleNo evidence for association of the dysbindin gene [DTNBP1] with schizophrenia in an Irish population-based study Schizophr Res 60 167–172 Occurrence Handle10.1016/S0920-9964(02)00527-3

    Article  Google Scholar 

  • JA Morris G Kandpal L Ma CP Austin (2003b) ArticleTitleDISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation Hum Mol Genet 12 1591–1608 Occurrence Handle1:CAS:528:DC%2BD3sXkvVSmsbg%3D Occurrence Handle10.1093/hmg/ddg162

    Article  CAS  Google Scholar 

  • T Numakawa Y Yagasaki T Ishimoto T Okada T Suzuki N Iwata N Ozaki T Taguchi M Tatsumi K Kamijima RE Straub DR Weinberger H Kunugi R Hashimoto (2004) ArticleTitleEvidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia Hum Mol Genet 13 2699–2708 Occurrence Handle15345706 Occurrence Handle1:CAS:528:DC%2BD2cXovVOis7c%3D Occurrence Handle10.1093/hmg/ddh280

    Article  PubMed  CAS  Google Scholar 

  • MJ Owen NM Williams MC O’Donovan (2004) ArticleTitleThe molecular genetics of schizophrenia: new findings promise new insights Mol Psychiatry 9 14–27 Occurrence Handle14581932 Occurrence Handle1:CAS:528:DC%2BD3sXhtVWhtr7F Occurrence Handle10.1038/sj.mp.4001444

    Article  PubMed  CAS  Google Scholar 

  • Y Ozeki T Tomoda J Kleiderlein A Kamiya L Bord K Fujii M Okawa N Yamada ME Hatten SH Snyder CA Ross A Sawa (2003) ArticleTitleDisrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth Proc Natl Acad Sci USA 100 289–294 Occurrence Handle12506198 Occurrence Handle1:CAS:528:DC%2BD3sXktlOmsQ%3D%3D Occurrence Handle10.1073/pnas.0136913100

    Article  PubMed  CAS  Google Scholar 

  • V Parikh AV Terry MM Khan SP Mahadik (2004) ArticleTitleModulation of nerve growth factor and choline acetyltransferase expression in rat hippocampus after chronic exposure to haloperidol, risperidone, and olanzapine Psychopharmacology (Berl) 172 365–374 Occurrence Handle1:CAS:528:DC%2BD2cXis1eksrs%3D Occurrence Handle10.1007/s00213-003-1669-6

    Article  CAS  Google Scholar 

  • N Sawamura T Sawamura-Yamamoto Y Ozeki CA Ross A Sawa (2005) ArticleTitleA form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse Proc Natl Acad Sci USA 102 1187–1192 Occurrence Handle15657124 Occurrence Handle1:CAS:528:DC%2BD2MXhtFCit7s%3D Occurrence Handle10.1073/pnas.0406543102

    Article  PubMed  CAS  Google Scholar 

  • SG Schwab M Knapp S Mondabon J Hallmayer M Borrmann-Hassenbach M Albus B Lerer M Rietschel M Trixler W Maier DB Wildenauer (2003) ArticleTitleSupport for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families Am J Hum Genet 72 185–190 Occurrence Handle12474144 Occurrence Handle1:CAS:528:DC%2BD3sXis1ynsA%3D%3D Occurrence Handle10.1086/345463

    Article  PubMed  CAS  Google Scholar 

  • RE Straub Y Jiang CJ MacLean Y Ma BT Webb MV Myakishev C Harris-Kerr B Wormley H Sadek B Kadambi AJ Cesare A Gibberman X Wang FA O’Neill D Walsh KS Kendler (2002) ArticleTitleGenetic variation in the 6p22.3 Gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia Am J Hum Genet 71 337–348 Occurrence Handle12098102 Occurrence Handle1:CAS:528:DC%2BD38XlvV2qtb4%3D Occurrence Handle10.1086/341750

    Article  PubMed  CAS  Google Scholar 

  • K Talbot WL Eidem CL Tinsley MA Benson EW Thompson RJ Smith CG Hahn SJ Siegel JQ Trojanowski RE Gur DJ Blake SE Arnold (2004) ArticleTitleDysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia J Clin Invest 113 1353–1363 Occurrence Handle15124027 Occurrence Handle1:CAS:528:DC%2BD2cXjvVOqs7k%3D Occurrence Handle10.1172/JCI200420425

    Article  PubMed  CAS  Google Scholar 

  • JX Tang J Zhou JB Fan XW Li YY Shi NF Gu GY Feng YL Xing JG Shi L He (2003) ArticleTitleFamily-based association study of DTNBP1 in 6p22.3 and schizophrenia Mol Psychiatry 8 717–718 Occurrence Handle12888799 Occurrence Handle1:CAS:528:DC%2BD3sXlvVGjtLs%3D Occurrence Handle10.1038/sj.mp.4001287

    Article  PubMed  CAS  Google Scholar 

  • A Van Den Bogaert J Schumacher TG Schulze AC Otte S Ohlraun S Kovalenko T Becker J Freudenberg EG Jonsson M Mattila-Evenden GC Sedvall PM Czerski P Kapelski J Hauser W Maier M Rietschel P Propping MM Nothen S Cichon (2003) ArticleTitleThe DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease Am J Hum Genet 73 1438–1443 Occurrence Handle14618545 Occurrence Handle1:CAS:528:DC%2BD2cXitlWn Occurrence Handle10.1086/379928

    Article  PubMed  CAS  Google Scholar 

  • EJ van den Oord PF Sullivan Y Jiang D Walsh FA O’Neill KS Kendler BP Riley (2003) ArticleTitleIdentification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families Mol Psychiatry 8 499–510 Occurrence Handle12808430 Occurrence Handle1:CAS:528:DC%2BD3sXksFKmur4%3D Occurrence Handle10.1038/sj.mp.4001263

    Article  PubMed  CAS  Google Scholar 

  • CS Weickert RE Straub BW McClintock M Matsumoto R Hashimoto TM Hyde MM Herman DR Weinberger JE Kleinman (2004) ArticleTitleHuman dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain Arch Gen Psychiatry 61 544–555 Occurrence Handle15184234 Occurrence Handle1:CAS:528:DC%2BD2cXlsFCju7Y%3D Occurrence Handle10.1001/archpsyc.61.6.544

    Article  PubMed  CAS  Google Scholar 

  • NM Williams A Preece DW Morris G Spurlock NJ Bray M Stephens N Norton H Williams M Clement S Dwyer C Curran J Wilkinson V Moskvina JL Waddington M Gill AP Corvin S Zammit G Kirov MJ Owen MC O’Donovan (2004) ArticleTitleIdentification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1) Arch Gen Psychiatry 61 336–344 Occurrence Handle15066891 Occurrence Handle1:CAS:528:DC%2BD2cXjslShtL0%3D Occurrence Handle10.1001/archpsyc.61.4.336

    Article  PubMed  CAS  Google Scholar 

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Chiba, S., Hashimoto, R., Hattori, S. et al. Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus. J Neural Transm 113, 1337–1346 (2006). https://doi.org/10.1007/s00702-005-0414-1

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