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Elucidation of mechanisms for spontaneous epileptic seizures in mice lacking μ3B, a subunit of the neuron-specific AP-3B complex

Research Project

Project/Area Number 15591208
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MORI Fumiaki  Hirosaki University, School of Medicine, Associate Professor, 医学部, 助教授 (60200383)

Co-Investigator(Kenkyū-buntansha) WAKABAYASHI Koichi  Hirosaki University, School of Medicine, Professor, 医学部, 教授 (50240768)
OKADA Motohiro  Hirosaki University, University Hospital, Lecturer, 医学部附属病院, 講師 (10281916)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsEpilepsy / Adaptor protein complex / μ3B / Synaptic vesicle formation / Hippocampus / Excitatory terminal / Inhibitory terminal / 抑制性終末 / CA3
Research Abstract

Adaptor protein (AP) complexes regulate the vesicular transport of cargo proteins in the late secretory and endocytic pathways. Mice lacking μ3B, a subunit of the neuron-specific AP-3B complex, suffered from spontaneous epileptic seizures after the age of 15 weeks.
In 2003, we performed morphometrical examinations of the CA1 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 2,4,6,8 and 16 weeks. The diameter of synaptic vesicles in excitatory terminals in KO was smaller than that in WT at the ages of 4,6 and 8 weeks, but not at the ages of 2 and 16 weeks. The densities of synaptic vesicles in both terminals in KO were lower than those in WT.
In 2004, we performed morphometrical examinations of the CA3 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 4,6,8 and 16 weeks, but not at the age of 2 weeks. On the other, the diameter of synaptic vesicles in mossy fiber terminals in KO was larger than that in WT at the ages of 2-16 weeks. The densities of synaptic vesicles in the mossy fiber terminals, but not the inhibitory, in KO were lower than those in WT.
It is possible that the imbalance between excitatory and inhibitory inputs to the hippocampus evokes epileptic seizures in this model.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (5 results)

All 2004 Other

All Journal Article (5 results)

  • [Journal Article] Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.2004

    • Author(s)
      Nakatsu F, Okada M, Mori F et al.
    • Journal Title

      J Cell Biol 167

      Pages: 293-302

    • NAID

      120004898419

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.2004

    • Author(s)
      Nakatsu F, Okada M, Mori F, et al.
    • Journal Title

      J Cell Biol 167-2

      Pages: 293-302

    • NAID

      120004898419

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.2004

    • Author(s)
      Nakatsu F, Okada M, Mori F et al.
    • Journal Title

      Journal of Cell Biology 167・2

      Pages: 293-302

    • NAID

      120004898419

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus.

    • Author(s)
      Mori F at al.
    • Journal Title

      Epilepsy Res (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epileptieus

    • Author(s)
      Mori F, et al.
    • Journal Title

      Epilepsy Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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