Enhancement of the function of aged synapses and its mechanism

• Project/Area Number: 09480226
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Metropolitan Institute of Gerontology
• Principal Investigator: ANDO Susumu Tokyo Metropolitan Institute of Gerontology, Department of Membrane Biochemistry, Head, 生態膜部門, 副所長 (30073000)
• Project Period (FY): 1997 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥6,200,000 (Direct Cost: ¥6,200,000); Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
• Keywords: Brain / Synapse / Aging / Sialic acid / Ganglioside / Acetylcholine / Calcium channel / Long-term potentiation / コリン取込み

Research Abstract

We have found in our previous studies that the hypofunction of the aged brain is caused by decreased synaptic transmission, and that the diminished transmission is due to decreased CaィイD12+ィエD1influx through voltage-dependent calcium channels. Based on these findings, we aimed to enhance the synaptic transmission of the aged brain in this study. (1) Gangliosides enriched on synaptic membranes were examined for their effects on CaィイD12+ィエD1influx. Ganglioside, GM1 or GQ1b, increased the depolarization-induced acetylcholine release from synaptosomes. This effect was proved to be due to enhanced efficacy of calcium channels. (2) Long-term potentiation as a marker of synaptic plasticity was enhanced by ganglioside GM1 or GQ1b. (3) In the attempt to apply the ganglioside effects on human cases, sialyl compounds, ganglioside analognes, of smaller molecular weight were speculated to be superior to natural gangliosides. Sialyl cholesterol was found to enhance the synaptic transmission.

Research Products

• [Publications] Nakamura,H., Ohashi Y., Kobayashi S.,Ando S.: "Age-changes of brain synapses and synaptic plasticity in response to an enriched environment"J. Neurosci. Res.. 56. 307-315 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakamura, H. , Ohashi Y., Kobayashi S., Ando S.: "Age-changes of brain synapses and synaptic plasticity in response to an enriched environment"J. Neurosci. Res.. 48(10). 73-80 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakamura H., Kobayashi S., Ohashi Y. and Ando S.: "Age-changes of brain synapses and synaptic plasticity in response to an enriched environment"J. Neurosci. Res.. 56. 307-315 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakamura H.,Kobayasi S.,Ohashi Y. and Ando S.: "Age-changes of brain synapses and synaptic plasticity in response to an enriched environment"J. Neurosci. Res.. 56. 307-315 (1999)
• [Publications] 安藤進: "老化脳と脂質栄養"日本油化学会誌. 48(10). 73-80 (1999)
• [Publications] Ando S,Tanaka Y,Waki H et al.: "Gangliosides and sialylcholesterol as modulators of synaptic functions" Ann.NY Acad.Sci.845. 232-239 (1998)
• [Publications] Suzuki H,Park S J,Tamura M.and Ando S: "Effect of the long-term feeding of dietary lipids on the learning ability,fatty acid composition of brain stem" Mech.Age.Develop.101. 119-128 (1998)
• [Publications] Furuse H,Waki H,Kato H,And S et al.: "Effect of mono-and tetra-sialogangliosides,GMI and GOIb,on long-term potentiation in the CA1 hippocampal neurons" Exp.Brain Res.123. 307-314 (1998)
• [Publications] Nakamura H,Kobayashi S,Ohashi Y,Ando S: "Age-changes of brain synapses and synaptic plasticity in response to an enriched environment" J.Neurosci.Res.(in press).
• [Publications] Inagaki N.,Goto H.,Ando S.et al.: "Spatial patterns of Ca signals define intracellular distribution of a signaling by Ca/calmodulin-dependent protein kinase II" J.Biol.Chem.272. 25195-25199 (1997)
• [Publications] Tanaka Y.,Waki H.,Kon K.and Ando S.: "Gangliosides enhance KCL-induced Ca influx and acetylcholine release in brain synaptosomes"