Identification of factors involving modulation of learning and memory function by brain neuropeptide, nociceptin and its related compounds

脑神经肽、伤害感受肽及其相关化合物调节学习记忆功能相关因素的鉴定

• 批准号: 12672230
• 负责人: HIRAMATSU Masayuki
• 金额: $ 1.92万
• 依托单位: Meijo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672230/
• 关键词: nociceptin; dynorphin A; learning and memory; opioid receptor; hippocampus; β-amyloid peptide; prodynorphin mRNA; prepronociceptin mRNA; β-amyloid peptide(25-35); 抗侵害作用; ノシセプチン; ノシスタチン; ダイノルフィン; 受動的回避学習

We previously reported that nociceptin and dynorphin A (1-13) improved impairment of learning and/or memory in several animal models. Furthermore, κ-opioid receptor agonists and (-)-nicotine prevented neurodegenerative damage induced by ischemia or β-amyloid peptide (25-35). In this study, we tested whether a κ-opioid receptor agonist, U-50,488H prevents delayed memory impairment induced by β-amyloid peptide (25-35) and changes of prepronociceptin mRNA, prodynorphin mRNA and α7 type nicotinic acetylcholine receptor mRNA. Seven days after β-amyloid peptide (25-35) treatment, memory impairment was prevented, and 10 days after β-amyloid peptide (25-35), there was no change in prepronociceptin mRNA, prodynorphin mRNA or α7 type nicotinic acetylcholine receptor mRNA expression in the hippocampus. These mRNA expressions were significantly decreased when U-50,488H was administered 1 hr before, but not 1 hr after β-amyloid peptide (25-35) treatment. In conclusion, activation of the κ-opioid system may produce neuroprotective effects on β-amyloid peptide (25-35)-induced toxicity, and may be involved in the long-lasting changes of these mRNA expressions.

我们先前报道说，在几种动物模型中，NociTptin和Dynorphin A（1-13）改善了学习和/或记忆的损害。此外，κ阿片受体激动剂和（ - ） - 尼古丁预防了缺血或β-淀粉样蛋白肽引起的神经退行性损伤（25-35）。在这项研究中，我们测试了κ-阿普尼受体激动剂U-50,488H是否可以防止β-淀粉样蛋白肽（25-35）诱导的延迟记忆障碍以及前脑膜炎蛋白mRNA，prodynorphin mRNA和prodynorphin mRNA和α7型烟碱乙酰胆碱受体mRNA的变化。 β-淀粉样蛋白肽（25-35）治疗后7天，预防记忆障碍，在β-淀粉样蛋白肽（25-35）后10天，前脑膜炎摄影mRNA，prododynorphin mRNA或α7型烟碱乙酰胆碱受体mRNA在Hhippippoppampus中没有变化。当U-50,488H之前1小时施用U-50,488H时，这些mRNA表达显着改善，但在β-淀粉样蛋白肽（25-35）处理后1小时不高1小时。总之，κ阿片类系统的激活可能会对β-淀粉样蛋白肽（25-35）诱导的毒性产生神经保护作用，并可能参与这些mRNA表达的持久变化。

项目成果

Masayuki Hiramatsu, Kaori Inoue, and Tsutomu Kameyama: "DynorphinA-(1-13) and (2-3) improve β-amyloid peptide-induced amnesia in mice"NeuroReport. 11 (3). 431-435 (2000)

Masayuki Hiramatsu、Kaori Inoue 和 Tsutomu Kameyama：“强啡肽 A-(1-13) 和 (2-3) 改善 β-淀粉样肽诱导的小鼠遗忘症”NeuroReport 11 (3)。

Masayuki Hiramatsu: "Effects of repeated administration of (-)-nicotine on AF64A-induced learning and memory impairment in rats"J.Neural Transm.. 109(3). 361-375 (2002)

Masayuki Hiramatsu：“重复施用 (-)-尼古丁对 AF64A 诱导的大鼠学习和记忆障碍的影响”J.Neural Transm.. 109(3)。

Masayuki Hiramatsu, Kaori Inoue, Akihiro Ambo, Yusuke Sasaki, Tsutomu Kameyama: "Long-lasting anitinociceptive effects of a novel dynorphin analogue, Tyr-D-Ala-Phe-Leu-Argψ(CH_2NH)Arg-NH_2, in mice"Brit. J. Pharmacol.. 132 (8). 1948-1956 (2001)

Masayuki Hiramatsu、Kaori Inoue、Akihiro Ambo、Yusuke Sasaki、Tsutomu Kameyama：“新型强啡肽类似物 Tyr-D-Ala-Phe-Leu-Argψ(CH_2NH)Arg-NH_2 对小鼠的持久抗伤害感受作用”Brit。 J.药理学.132（8）1948-1956（2001）。

Masayuki Hiramatsu: "Des-tyrosinel dynorphin A-(2-13) improves carbon monoxide-induced impairment of learning and memory in mice"Brain Res.. 859/2. 303-310 (2000)

Masayuki Hiramatsu：“去酪氨酸强啡肽 A-(2-13) 改善一氧化碳诱导的小鼠学习和记忆障碍”Brain Res.. 859/2。

Masayuki Hiramatsu and Kaori Inoue: "Des-tyrosine1 dynorphin A-(2-13) improves carbon monoxide-induced impairment of learning and memory in mice"Brain Res.. 859 (2). 303-310 (2000)

Masayuki Hiramatsu 和 Kaori Inoue：“Des-tyrosine1 强啡肽 A-(2-13) 改善一氧化碳诱导的小鼠学习和记忆障碍”Brain Res.. 859 (2)。