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Does catecholaminergic agonist modulate gene expression in the brain, via DNA methylation?

Research Project

Project/Area Number 14570906
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionTohoku University

Principal Investigator

NUMACHI Yohtaro  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (00261636)

Co-Investigator(Kenkyū-buntansha) SORA Ichiro  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40322713)
NUMACHI Sumiko (YOSHIDA Sumiko)  Sendai University, Gymnastics faculty, Professor, 体育学部, 教授 (50261532)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsPsychostimulant / Drug Abuse / Schizophrenia / gene expression / Methylation / Synaptic proteins / reversibility
Research Abstract

Methamphetamine (MAP) is a potent catecholaminergic agonist as well as abused drug, which can cause psychotic state resembles schizophrenia. It is postulated that long-term alterations in gene expression is induced by MAP, in the brains of MAP-treated animals. Methylation on cytosine residues of dinucleotides sequence 5'-C G-3' on DNA can strongly inhibit expression of downstream gene. We previously found alterations in the expression of DNA methltransferase I (DnmtI) mRNA in the brain of MAP-treated rat. According to these results, we studied about (1) and (2) as below, in this project.
(1)MAP decreased hippocampal mRNA for corticosterone receptor in Fischer 344 rat, which showed high sensitivity to MAP. On the other hand, there was no change in corticosterone receptor rnRNA in the hippocampus of Lewis rat, with low sensitivity to MAP. It is reported that actions of MAP is partially via corticosterone and corticosterone receptor can inhibit gene expression by DNA methylation. Our results suggest that differences between Fischer 344 and Lewis in their sensitivity to MAP is related to transcriptional regulation by DNA methylation (kabbaj, M., Yoshida, S., Nuinachi, Y., et al. 2003).
(2)MAP did not alter expression of Dnmt2 mRNA in the brain of Wister rat. But reelin mRNA in the frontal cortex of Wister rat decreased 3 hrs after MAP, and thereafter returned to normal level. Recently, in the frontal cortex of schizophrenic patient, decrease in reelin mRNA and increase in Dnmt I mRNA were found (Veldic, 2004). So, MAP-induced decrease in reelin mRNA in the frontal cortex of rat might be related to psychotomimetic action of MAP (Numachi, Y., Yoshida, S., Yamashita, M., et al. in press).

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Shen H, Numachi Y, Yoshida S, et al.: "Electroconvulsive shock increases serotonin transporter in the rat frontal cortex."Neurosci Lett. 341(2). 170-172 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kabbaj M, Yoshida S, Numachi Y et al.: "Methamphetamine differentially regulates hippocampal glucocorticoid and mineralocorticoid receptors mRNAs in Fisher and Lewis rats."Brain Res Mol Brain Res. 117(1). 8-14 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numachi Y, Yoshida S, et al.: "Psychostimulant alters expression of DNA methyltransferase mRNA in the rat brain."Ann N Y Acad Sci. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 沼知陽太郎, 吉田寿美子, 曽良一郎: "うつと不安の共通因子"Bulletin of Depression and Anxiety. 1. 8-11 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 沼知陽太郎, 吉田寿美子, 曽良一郎, 佐藤光源: "ストレス逆耐性仮説"こころの臨床. 17巻増刊号(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 沼知陽太郎, 吉田寿美子, 曽良一郎, 佐藤光源: "覚醒剤の体内動態と脳内分布"Clinical Neuroscience. 22(6)(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 佐藤光源, 梶井靖, 菊池周一, 沼知陽太郎, 西川徹: "脳科学研究の現状と課題(杉田秀夫, 高橋清久編)"(株)じほう, 東京. 324 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shen H, Numachi Y, Yoshida S, et al.: "Electroconvulsive shock increases serotonin transporter in the rat frontal cortex"Neurosci. 341(2). 170-172 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kabbaj M, Yoshida S, Numachi Y, et al.: "Methamphetamine differentially regulates hippocampal glucocorticoid and mineralocorticoid receptor mRNAs in Fischer and Lewis rats"Brain Res Mol Brain Res. 117(1). 8-14 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numachi Y, Yoshida S, et al.: "Psychostimulant alters expression of DNA methyltransferase mRNA in the rat brain"Ann N Y Acad Sci. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numachi Y, Yoshida S, Sora I.: "Common aspects between depression and anxiety (in Japanese)"Bulettin of Depression and Anxiety. 1. 8-11 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numachi Y, Yoshida S, Sora I, Sato M.: "Stress-induced sensitization hypothesis for schizophrenia (in Japanese)"Kokoro no Rinsyo. 17 (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Numachi Y, Yoshida S, Sora I, Sato M.: "Pharmacokinetics and Brain distribuion of psychostimulants (in Japanese)"Clinical Neurocience. 22(6) (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato M, Kajii Y, Kikuchi S, Numachi Y, Nishikawa T.: "Current issues for brain research (Sugita H., Takahashi K, eds) (in Japanese)"Jiho Inc, Tokyo. 287-299 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shen H, Numachi Y, Yoshida S, et al.: "Electroconvulsive shock increases serotonin transporter in the rat frontal cortex"Neurosci Lett. 341(2). 170-172 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kabbaj M, Yoshida S, Numachi Y, et al.: "Methamphetamine differentially regulates hippocampal glucocorticoid and mineralocorticoid receptors mRNAs in Fisher and Lewis rats"Brain Res Mol Brain Res. 117(1). 8-14 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Numachi Y, Yoshida S, et al.: "Psychostimulant alters expression of DNA methyltransferase mRNA in the rat brain"Ann N Y Acad Sci. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 沼知陽太郎, 吉田寿美子, 曽良一郎: "うつと不安の共通因子"Bulletin of Depression and Anxiety. 1. 8-11 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 沼知陽太郎, 吉田寿美子, 曽良一郎, 佐藤光源: "ストレス逆耐性仮説"こころの臨床. 17(増刊号)(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 沼知陽太郎, 吉田寿美子, 曽良一郎, 佐藤光源: "覚醒剤の体内動態と脳内分布"Clinical Neuroscience. 22(6)(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 佐藤光源, 梶尾靖, 菊池周一, 沼知陽太郎, 西川徹: "脳科学研究の現状と課題(杉田秀夫,高橋清久編)"(株)じほう,東京. 324 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuoka, H., Takahashi, T., Sasaki, M., Yoshida, S., Numachi, Y., et al.: "The long-term course of seizure susceptibility in two patients with juvenile myoclonic epilepsy"Seizure. 11. 126-130 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shen, H., Numachi, Y, et al.: "Electroconvulsive shock increases serotonin transporter in the rat frontal cortex"Neuroscience Letters. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤山航, 堀内健太郎, 本多奈美, 沼知陽太郎, 他: "clobazam投与によって強制正常化を呈した前頭葉てんかんの一例"脳と精神の医学. 13. 427-431 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 佐藤光源, 梶井靖, 菊池周一, 沼知陽太郎, 他: "脳科学研究はここまで進んだ(高橋清久編)"(株)じほう,東京(印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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