Establishment and estimation of pharmacological bioassay system for therapeutic drugs of aging in central nervous system.

中枢神经系统衰老治疗药物药理生物测定体系的建立与评价

• 批准号: 07557148
• 负责人: NOMURA Yasuyuki
• 金额: $ 9.41万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 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-07557148/
• 关键词: learning; memory; aging; dementia; acetylcholine (ACh); muscarinic ACh receptor; muscarinic antagonist; SAM mouse; 記憶・学習; 丹参; lithospermic acid B; SAMP8系マウス; Moris's water maze; プロテインキナーゼC; [^3H]PDBu結合; 空間認知機能改善作用

To clarify the physiological roles of muscarinic acetylcholine (mACh) receptor subtypes, M1 and M2, on learning and memory, we examined the effects of three antagonists, atropine (non-selective), pirenzepine (M1 selective) and 11-[[2[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one, AF-DX 116 (M2 selective), on stpe-through passive avoidance tasks in mice. Pre-training (5min before) administration of atropine (1-40 nmol) and pirenzepine (10 and 40 nmol) shortened the response latency in retention tests at 14 d after acquisition training. Pre-test (5min befor) and post-training (immediately after the acquisition) administration of atropine slightly but not significantly impaired retention scores. The administration of AF-DX 116 did not apparently affect the scores in any of tests. Thus, the M1 receptor subtype coupling systemes seem to be more important in the acquisition-consolidation process rather than in the retrieval process.

为了阐明毒蕈碱型乙酰胆碱（mACh）受体亚型M1和M2在学习和记忆中的生理作用，我们研究了三种拮抗剂阿托品（阿托品）（非选择性），哌仑西平（M1选择性）和11-[[2[[（二乙基氨基）甲基]-1-哌啶基]乙酰基]-5，11-二氢-6H-吡啶并[2，3-B][1，4]苯并二氮杂卓-6-酮，AF-DX 116（M2选择性）对小鼠的stpe-through被动回避任务的影响。训练前5 min给予阿托品（1-40 nmol）和哌仑西平（10和40 nmol）可缩短获得训练后14 d的反应潜伏期。测试前（5分钟前）和训练后（收购后立即）给予阿托品轻微但不显着损害保留分数。AF-DX 116的施用对任何测试中的分数没有明显影响。因此，M1受体亚型偶联系统似乎在获取-巩固过程中比在检索过程中更重要。

项目成果

野村靖幸: "医学のあゆみ 別冊「NOのすべて」脳グリアiNOSの発現調節機構" 医歯薬出版, 5 (1996)

野村康之：“医学史特别版‘关于NO’：大脑胶质细胞iNOS的表达调节机制”石药出版社，5（1996）

Arima, T.: "Kyotorphin (L-tyrosyl-arginine) as a possible substrate for inducible nitric oxide synthase in rat glial cells" Neurosci, Lett. 212. 1-4 (1996)

Arima，T.：“Kyotorphin（L-酪氨酰精氨酸）作为大鼠神经胶质细胞中诱导型一氧化氮合酶的可能底物”Neurosci，Lett。

Yasuhiro Itano: "Regulation of Bcl-2 protein expression in human neuroblastoma SHSY-5Y cells : positive and negative effects of protein kinase C and A, respectively." Journal of Neurochemistry. 67. 131-137 (1996)

Yasuhiro Itano：“人神经母细胞瘤 SHSY-5Y 细胞中 Bcl-2 蛋白表达的调节：分别是蛋白激酶 C 和 A 的正面和负面影响。”

Yasuyuki Nomura: "Neuronal apoptosis by glial NO : Involvement of inhibition of glyceraldehyde-3-phosphate dehydrogenase." Human Cell. 9. 205-214 (1996)

Yasuyuki Nomura：“神经胶质细胞 NO 导致的神经细胞凋亡：涉及 3-磷酸甘油醛脱氢酶的抑制。”

Ohnuki, T.: "Effects of selective muscarinic antagonists, Pirenzepine and AF-DX 116, on passive avoidance tasks in mice" Biol.Pharm.Bull. 19. 814-818 (1996)

Ohnuki, T.：“选择性毒蕈碱拮抗剂哌仑西平和 AF-DX 116 对小鼠被动回避任务的影响”Biol.Pharm.Bull。