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Aging of voltage-dependent calcium channels in brain synapses

Research Project

Project/Area Number 07458208
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

ANDO Susumu  Tokyo Metropolitan Institute of Gerontology, Department of Membrane Biochemistry, Research Director, 研究部長 (30073000)

Co-Investigator(Kenkyū-buntansha) 田中 康一  (財)東京都老人総合研究所, 生体膜部門, 主任研究員 (40101258)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordsaging / brain / synapse / acetylcholine / calcium channel / ganglioside
Research Abstract

We have found age-related changes in synaptic functions, that is, decreased release of acetylcholine from synapses and diminished influx of calcium ion through voltage-dependent calcium channels. Furthermore, the efficacy of calcium channels were shown to be restored with sialyl compounds.
The activities of acetylcholine synthesis and rlease were examined using synaptosomes. It wss found that the synthetic rate of acetylcholine was maintained the same in aged synapses as in young, and that acetylcholine release evoked by depolarization was decreased. It is known that the exositosis of transmitters is triggered by calcium ion coming in through calcium channels. In fact, calcium influx was found to decrease in aged synaptosomes as monitored using Fura-2. Thus, these observations may indicate that dimished influx of calcium ion through calcium channesl underly the decreased release of acetylcholine in aged synapses.
To restore the decreased release of acetylcholine, the enhancement of calcium influx was attempted by modifying the channel efficacy. Sialyl compounds such as gangliosides and their synthetic analogues which have high affinity to calcium have been found to enhance calcium influx. These results suggest that sialyl compounds may restore the decreased synaptic functions in aging.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Tanaka Y,Hasegawa A & Ando S: "Impaired synaptic functions with aging as characterized by decreased calcium influx and acetylcholine release" Journal of Neuroscience Research. 43. 63-70 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka Y & Ando S: "Modulation of chokinergic synaptic functions by sialylcholesterol" Glycoconjugate Journal. 13. 321-326 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 安藤進: "脳機能とガングリオシド" 共立出版, 162 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka Y,Hasegawa A & Ando S: ""Impaired synaptic functions with aging as characterized by decreased calcium influx and acetylcholine release"" J.Neurosci. Res.43. 63-70 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka Y & Ando S: ""Modulation of cholinergic synaptic functions by sialylcholesterol"" Glycoconjugate J.13. 321-326 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka Y,Hasegawa A & Ando S: "Impaired synaptic functions with aging as chatacterized by decreased calcium influx and acetylcholine release" Journal of Neuroscience Research. 43. 63-70 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka Y & Ando S: "Modulation of cholinergic synaptic functions by sialylcholesterol" Glycoconjugate Journal. 13. 321-326 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 安藤進: "脳機能とガングリオシド" 共立出版, 162 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Saito, M.: "Characterization of sialidase activity in mouse synapticplasma membranes and its age-related changes" J. Neurosci. Res.40. 401-406 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka, Y.: "Impaired synaptic functions with aging as characterized by decreased calcium influx and acetylecholine release" J. Neurosci. Res.43. 63-70 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 鈴木康夫・安藤進: "ガングリオシド研究法I,II 生物化学実験法35" 学会出版センター, 532 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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