权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of relationship between vasopressin fragment analog -induced mnemonic effect and NMDA receptors

加压素片段类似物诱导记忆效应与NMDA受体关系分析

基本信息

批准号：
18592040
负责人：
SATO Tomoaki
金额：
$ 2.48万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592040/
关键词：
vasopressin vasopressin fragment vasooressin fragment analg NMDA receptor learning memory Cyclooxygenase glutamate receptor PCR Morris Water Maze 記憶増強

项目摘要

1. NMDA receptor activation and vasopressin fragmentIn recent years, it is reported that activation of cyclooxygenase (COX) increased NMDA receptors activity. Therefore, we investigated relationships between COX and learning and/or memory. To examine the participation of COX-3 on memory formation, water maze performance was studied in mice treated with acetaminophen (AAP), phenacetin (PHE) or other COX inhibitors. Mice received intraperitoneal injections of drugs immediately after each training session. The administration of AAP[302.3 mg/kg (over the IC_<50> for COX-2) ]or PHE[179.2 mg/kg (IC (50) for COX-2) ]and of a non-specific (indomethacin : 20 mg/kg) or specific COX-2 (NS-398 : 20 mg/kg) inhibitor impaired the performance in hidden platform (HP) not visible platform (VP) tasks, whereas the low-dose (15.1 mg/kg) AAP facilitated performance in HP and VP tasks. The facilitation of performance by the low-dose AAP was reversed by co-administration with a 5-HT_1/2 receptor antagonist ( … More methysergide : 0.47 mg/kg). The middle-dose[69.5 mg/kg (IC_<50> for COX-3) ]AAP, the low-dose PHE[17.9 mg/kg (IC_<50> for COX-3) ],and a specific COX-1 inhibitor (piroxicam : 10-20 mg/kg) did not influence performance in either task. These results suggest that administration of selective COX-3 inhibitors modulated cognitive function. The memory impairment and the facilitation of performance could involve endogenous COX-2 and serotonergic neuronal activity, respectively, but not COX-3.2. COX and mnemonic effect induced by vasopressin fragmentWe investigated the effect of administration of inhibitors of each of the arachidonic acid metabolism pathways and co-administration of NC-1900, a fragment analog of arginine vasopressin, with these inhibitors could influence latency on the step-through passive avoidance task. Intracerebroventricular (i.c.v.) administration of nordihydroguaiaretic acid (NDGA) (10 μg), a phospholipase A_2 (PLA_2) and lipoxygenase (LOX) inhibitor, and of arachidonyl trifluoromethyl ketone (ATK) (10μg), a specific PLA2 inhibitor caused reductions in latency on the retention trial (Ret.). The i.c.v. administration of either of baicalein, a 12-LOX inhibitor, or AA-861, a 5-LOX inhibitor, did not influence the latency. I.p. administration of indomethacin (IND: 20 mg/kg), a non-specific COX inhibitor, or NS-398 (10 mg/kg), a specific COX-2 inhibitor, impaired performance on Ret., while piroxicam, a specific COX-1 inhibitor, did not. S.c. administration of NC-1900 (0.1 ng/kg) ameliorated the reduction of latency caused by NDGA, ATK, IND, or NS-398. These results suggested that the ameliorating effect of NC-1900, in part, is due to mimicking of the effects of metabolites of the COX-2 pathway.3. ConclusionAbove-mentioned, it is suggested that cyclooxygenase pathway participate in activation of NMDA receptor, and that the activation of NMDA receptor may induce a mnemonic effect on learning and memory. Less

1. NMDA受体激活与加压素片段近年来，有研究表明，环氧化酶（cyclooxygenase，考克斯）的激活可增加NMDA受体的活性。因此，我们研究了考克斯和学习和/或记忆之间的关系。为了检查考克斯-3对记忆形成的参与，在用对乙酰氨基酚（AAP）、非那西丁（PHE）或其它考克斯抑制剂处理的小鼠中研究水迷宫表现。小鼠在每次训练后立即接受腹膜内注射药物。AAP[302.3 mg/kg（超过<50>考克斯-2的IC_）]或PHE[179.2 mg/kg（考克斯-2的IC（50））]和非特异性（吲哚美辛：20 mg/kg）或特异性考克斯-2（NS-398：20 mg/kg）抑制剂的给药损害了隐藏平台（HP）和不可见平台（VP）任务中的表现，而低剂量（15.1 mg/kg）AAP促进了HP和VP任务中的表现。与5-HT_1/2受体拮抗剂（ ...更多信息麦角新碱：0.47 mg/kg）。中剂量[69.5 mg/kg（IC_<50>for考克斯-3）]AAP、低剂量PHE[17.9 mg/kg（IC_<50>for考克斯-3）]和特异性考克斯-1抑制剂（吡罗昔康：10-20 mg/kg）均不影响两项任务的表现。这些结果表明，选择性考克斯-3抑制剂的管理调制的认知功能。记忆障碍和操作的易化可能分别涉及内源性考克斯-2和多巴胺能神经元活性，但不涉及考克斯-3。考克斯与加压素片段诱导的记忆效应我们研究了花生四烯酸代谢途径的抑制剂以及精氨酸加压素片段类似物NC-1900与这些抑制剂共同给药对避暗被动回避任务潜伏期的影响。脑室内（i. c. v.）给予磷脂酶A_2（PLA_2）和脂氧合酶（LOX）抑制剂去甲二氢愈创木酸（NDGA）（10 μg）和特异性PLA_2抑制剂花生四烯基三氟甲基酮（ATK）（10μg）可使保留试验的潜伏期缩短（Ret.）。i. c. v.给药黄芩素（一种12-LOX抑制剂）或AA-861（一种5-LOX抑制剂）不影响潜伏期。腹膜内注射消炎痛（IND：20 mg/kg）（一种非特异性考克斯抑制剂）或NS-398（10 mg/kg）（一种特异性考克斯-2抑制剂），会损害Ret的表现。，而特异性考克斯-1抑制剂吡罗昔康则没有。S.C. NC-1900（0.1ng/kg）的给药改善了由NDGA、ATK、IND或NS-398引起的潜伏期的减少。这些结果表明NC-1900的改善作用部分是由于模拟了考克斯-2途径的代谢产物的作用。结论环氧化酶通路参与NMDA受体的激活，NMDA受体的激活可能对学习记忆产生促进作用。少