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Research for modulation of expression of serotonin transporter and its involvement in mental disorder

Research Project

Project/Area Number 09670091
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKOBE UNIVERSITY

Principal Investigator

SAITO Naoaki  Kobe University, Biosignal Research Center, Professor, バイオシグナル研究センター, 教授 (60178499)

Co-Investigator(Kenkyū-buntansha) SAKAI Norio  Kobe University, Biosignal Research Center, Assistant Professor, バイオシグナル研究センター, 助手 (70263407)
SHIRAI Yasuhito  Kobe University, Biosignal Research Center, Assistant Professor, バイオシグナル研究センター, 助手 (60263399)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsserotonin / transporter / interferon / phosphorylation / depression / synapse / electron microscopy / 脱リン酸化 / 変異体 / COS-7細胞
Research Abstract

We examined the regulatory mechanism of serotonin transporter and the involvement of serotonin transporter (SET) in depression to elucidate the function role of SET in mental disorder.
1. Regulation of SET by phosphorylation. The regulation of SET expressed in COS7 cells by the activation of protein kinase C with phorbol ester or by inhibition of protein phosphatases with calyculin A was examined. Both treatment decreased the activity of SET with a reduction in Vmax without affecting Km. Site-directed mutagenesis of five putative PKC phosphorylation sites in SET revealed that these inhibitory modulation of SET activity did not act via direct phosphorylation of SET by PKC.
2. Immunocytochemical localization of SET.The cellular and intracellular localization of SET was examined by immunocytochemistry. SET was localized in the varicose nerve fibers and nerve terminals but not in the cell bodies. Under electron microscopy, SET was seen around the synaptic vesicles as well as presynaptic membrane.
3. The effects of interferon-alpha and -gamma on the transcription of SET.Both SET mRNA and SET activity were increased by treatment with interferon-alpha and -gamma for 3 h. Treatment with dibutyryl cAMP also increased SET mRNA and SET activity. The level of SET mRNA was increased both in the midbrain and adrenal glands of mice which were treated with interferons for 3 h. These results suggest that the interferon-induced psychiatric side effects arise through regulation of serotonin transporter transcription and that the transcriptional regulation of the serotonin transporter is a possible neurochemical mechanism of affective disorders.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Morikawa,O.,他: "Effects of interferon-α and -γ on the transcriptional regulation of serotonin transporter." Eur.J.Pharmacol.349. 317-324 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakai N.他: "Modulation of serotonin transporter activity by a PKC activator and an inhibitor of type 1 and 2A serine/threonine phophatases." J.Neurochem.68. 2618-2624 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakai N.他: "Direct visualization of translocation of γ-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein." J.Cell Biol.139. 1465-1476 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakashita M.,他: "Effects of tricyclic and tetracyclic antidepressants on the three subtypes of GABA transporter." Neurosci.Res.29. 87-91 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishimura M.他: "Differential expression patterns of GABA transporters(GAT1-3)in the rat olfactory bulb." Mol.Brain Res.45. 268-274 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Obata H.他: "GABAergic neurotransmission in rat taste buds ; Immunocytochemical study for GABA and GABA transporter subtypes." Mol.Brain Res.49. 29-36 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hashimoto,T.他: "Isoform-specific redistribution of calcineurin Aα and Aβ in hippocampal CA1 region of Gerbil after transient ischemia." J.Neurochem.70. 1289-1298 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakai,M.他: "Amyloid beta Protein(25-35)Phosphorylates MARCKS through Tyrosine Kinase-Activated Protein Kinase C Signaling Pathway in Microglia." Eur.J.Pharmacol.(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohmori,S.他: "Three distinct mechanisms for translocation and activation of δ-subspecies of protein kinase C." Mol.Cell.Biol.18. 5263-5271 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shirai,Y.他: "Distinct effects of fatty acids on translocation of γ-and ε-protein kinase C." J.Cell.Biol.143. 511-521 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shirai,Y.他: "Subspecies specific targeting mechanism of protein kinase C." Jpn.J.Pharmacology.78. 411-417 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamamoto,H.,他: "Immunohistochemical localization of serotonin transporter in normal and colchicine treated rat brain." Neurosci.Res.32. 305-312 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hashimoto T.et al.: "Isoform-specific redistribution of calcineurin Aalpha and Abeta in hippocampal CA1 region of Gerbil after transient ischemia." J.Neurochem.70. 1289-1298 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morikawa, O.et al.: "Effects of interferon-alpha and -gamma on the transcriptional regulation of serotonin transporter." Eur.J.Pharmacol.349. 317-324 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakai N.et al.: "Modulation of serotonin transporter activity by a PKC activator and an inhibitor of type 1 and 2A serine/threonine phophatases." J.Neurochem. 68. 2618-2624 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakai N.et al.: "Direct visualization of translocation of gamma-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein." J.Cell Biol.139. 1465-1476 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakashita M.et al.: "Effects of tricyclic and tetracyclic antidepressants on the three subtypes of GABA transporter." Neurosci.Res.29. 87-91 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishimura M.et al.: "Differential expression patterns of GABA transporters (GAT1-3) in the rat olfactory bulb." Mol.Brain Res.45. 268-275 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Obata H.et al.: "GABAergic neurotransmission in rat taste buds ; Immunocytochemical study for GABA and GABA transporter subtypes." Mol.Brain Res.49. 29-36 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohmori, S.et al.: "Three distinct mechanisms for translocation and activation of delta-subspecies of protein kinase C." Mol.Cell.Biol.18. 5263-5271 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shirai, Y.et al.: "Distinct effects of fatty acids on translocation of gamma-and epsilon-protein kinase C." J.Cell.Biol.143. 511-521 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shirai, Y.et al.: "Subspecies specific targeting mechanism of protein kinase C." Jpn.J.Pharmacology. 78. 411-417 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamamoto, H., et al.: "Immunohistochemical localization of serotonin transporter in normal and colchicine treated rat brain." Neurosci.Res.32. 305-312 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakai, M.et al.: "Amyloid beta Protein (25-35) Phosphorylates MARCKS through Tyrosine Kinase-Activated Protein Kinase C Signaling Pathway in Microglia." J.Neurochem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murakami, N.et al.: "An association study of a polymorphsim of non-erythroid alpha-spectrin gene with schizophrenia." American Journal of Medical Genetics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hashimoto,T.他: "Isoform-specific redistribution of calcineurin Aα and Aβ in hippocampal CA1 region of Gerbil after transient ischemia." J.Neurochem.70. 1289-1298 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morikawa,O.他: "Effects of interferon-α and-γ on the transcriptional regulation of serotonin transporter." Eur.J.Pharmacol.349. 317-324 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohmori,S.他: "Three distinct mechanisms for translocation and activation of δ-subspecies of protein kinase C." Mol.Cell.Biol.18. 5263-5271 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shirai,Y.他: "Distinct effects of fatty acids on translocation of γ-and ε-protein kinase C." J.Cell.Biol.143. 511-521 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shirai,Y.他: "Subspecies specific targeting mechanism of protein kinase C." Jpn.J.Pharmacology.78. 411-417 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto,H.,他: "Immunohistochemical localization of serotonin transporter in normal and colchicine treated rat brain." Neurosci.Res.32. 305-312 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakai,M.他: "Amyloid beta protein(25-35)Phosphorylates MARCKS through Tyrosine Kinase-Activated Protein Kinase C Signaling Pathway in Microglia." J.Neurochem.(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Murakami,N.他: "An association study of a polymorphsim of non-erythroid α-spectrin gene with schizophrenia." American Journal of Medical Genetics.(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Morikawa,O.他: "Effects of interferon-α and -γ on the transcriptionai regulation of serotonin transporter." Eur.J.Pharmacol.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakai N.他: "Modulation of serotonin transporter activity by a PKC activator and an inhibitor of type 1 and 2A serine/threonine phophatases." J.Neurochem.68. 2618-2624 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakai N.他: "Direct visualization of translocation of γ-subspecies of protein kinase C in living cells using Fusion proteins with green fluorescent protein." J.Cell Biol.139. 1465-1476 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakashita M.,他: "Effects of tricyclic and tetracyclic antidepressants on the three subtypes of GABA transporter." Neurosci.Res.29. 87-91 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishimura M.他: "Differential expression patterns of GABA transporters (GAT1-3) in the rat olfactory bulb." Mol.Brain Res.45. 268-274 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Obata H.他: "GABAergic neurotransmission in rat taste buds; Immunocytochemical study for GABA and GABA transporter subtypes." Mol.Brain Res.49. 29-36 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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