Aging of voltage-dependent calcium channels in brain synapses

脑突触中电压依赖性钙通道的老化

• 批准号: 07458208
• 负责人: ANDO Susumu
• 金额: $ 4.22万
• 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: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07458208/
• 关键词: aging; brain; synapse; acetylcholine; calcium channel; ganglioside

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.

我们已经发现突触功能的年龄相关变化，即突触释放的乙酰胆碱减少和通过电压依赖性钙通道的钙离子内流减少。此外，唾液酸类化合物还能恢复钙通道的功能，用突触体检测乙酰胆碱合成和释放的活性。结果发现，老年突触乙酰胆碱合成速率与青年突触相同，去极化诱发的乙酰胆碱释放减少。已知递质的外生是由通过钙通道进入的钙离子触发的。事实上，钙内流被发现在老化的突触体中减少，如使用Fura-2监测的。因此，这些观察结果可能表明，钙离子通过钙通道的内流减少是衰老突触中乙酰胆碱释放减少的基础，为了恢复减少的乙酰胆碱释放，试图通过改变通道效率来增强钙内流。已发现对钙具有高亲和力的唾液酸化合物如神经节苷脂及其合成类似物可增强钙内流。这些结果表明，唾液酸化合物可能会恢复老化的突触功能下降。

项目成果

Tanaka, Y.: "Impaired synaptic functions with aging as characterized by decreased calcium influx and acetylecholine release" J. Neurosci. Res.43. 63-70 (1996)

Tanaka, Y.：“随着年龄的增长，突触功能受损，其特征是钙流入和乙酰胆碱释放减少”J. Neurosci。

安藤進: "脳機能とガングリオシド" 共立出版, 162 (1997)

安藤进：“脑功能和神经节苷脂”Kyoritsu Shuppan，162 (1997)

Saito, M.: "Characterization of sialidase activity in mouse synapticplasma membranes and its age-related changes" J. Neurosci. Res.40. 401-406 (1995)

Saito, M.：“小鼠突触质膜唾液酸酶活性的表征及其与年龄相关的变化”J. Neurosci。

Tanaka Y & Ando S: "Modulation of cholinergic synaptic functions by sialylcholesterol" Glycoconjugate Journal. 13. 321-326 (1996)

田中Y

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)

铃木康夫和安藤进：《神经节苷脂研究方法I、II生化实验方法35》学会出版中心，532（1995）