Enhancement of the function of aged synapses and its mechanism

衰老突触功能增强及其机制

• 批准号: 09480226
• 负责人: ANDO Susumu
• 金额: $ 3.97万
• 依托单位: Tokyo Metropolitan Institute of Gerontology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480226/
• 关键词: Brain; Synapse; Aging; Sialic acid; Ganglioside; Acetylcholine; Calcium channel; Long-term potentiation; コリン取込み

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.

我们在以前的研究中发现，老年脑功能低下是由于突触传递减少所致，而突触传递减少是由于通过电压依赖性钙通道的CaィイD12+ィエD1内流减少所致。基于这些发现，我们在本研究中旨在增强老年人大脑的突触传递。(1)观察突触膜上神经节苷脂对CaィイD12+ィエD1内流的影响。神经节苷脂、GM1或GQ1b可增加去极化诱导的突触体乙酰胆碱释放。这一作用被证明是由于钙通道的作用增强。(2)神经节苷脂GM1或GQ1b可增强突触可塑性的长时程增强。(3)在试图将神经节苷脂作用应用于人类病例中，分子量较小的唾液酸神经节苷脂类似物被推测为优于天然神经节苷脂。唾液酸脂被发现能增强突触传递。

项目成果

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)

Suzuki H，Park S J，Tamura M.和Ando S：“长期喂养膳食脂质对学习能力、脑干脂肪酸组成的影响”Mech.Age.Develop.101。

安藤進: "老化脳と脂質栄養"日本油化学会誌. 48(10). 73-80 (1999)

Susumu Ando：“大脑老化和脂质营养”，日本石油化学会杂志 48(10) (1999)。

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)

Furuse H、Waki H、Kato H 和 S 等人：“单唾液酸神经节苷脂和四唾液酸神经节苷脂、GMI 和 GOIb 对 CA1 海马神经元长期增强的影响”Exp.Brain Res.123。

Ando S,Tanaka Y,Waki H et al.: "Gangliosides and sialylcholesterol as modulators of synaptic functions" Ann.NY Acad.Sci.845. 232-239 (1998)

Ando S、Tanaka Y、Waki H 等人：“神经节苷脂和唾液酸胆固醇作为突触功能的调节剂”Ann.NY Acad.Sci.845。

Tanaka Y.,Waki H.,Kon K.and Ando S.: "Gangliosides enhance KCL-induced Ca influx and acetylcholine release in brain synaptosomes"

Tanaka Y.、Waki H.、Kon K. 和 Ando S.：“神经节苷脂增强 KCL 诱导的脑突触体中 Ca 离子流入和乙酰胆碱释放”