Department of Anatomy and Structural Biology, School of Medical Sciences, Brain Health and Repair Research Centre, University of Otago, Dunedin, New Zealand.
Neuroscience. 2010 Aug 25;169(2):794-811. doi: 10.1016/j.neuroscience.2010.05.004. Epub 2010 May 10.
Amyloid beta fragment 25-35 (Abeta(25-35)) is the neurotoxic domain of the full-length Abeta(1-42) and causes memory impairments in rodents. Recent research suggests that agmatine, decarboxylated arginine, has a neuroprotective role. This study investigated the effects of a single bilateral i.c.v. infusion of aggregated Abeta(25-35) (30 nmol) in a battery of behavioural tests conducted during the period 4-6 (Experiment 1) and 4-14 (Experiment 2) weeks post-Abeta(25-35) infusion, and evaluated the protective effect of agmatine (40 mg/kg) administered i.p. 30 min prior to Abeta(25-35) infusion and once daily for a further nine consecutive days. In Experiment 1, Abeta(25-35) rats with saline treatment were not impaired in the elevated plus maze and open field and mildly impaired in the reference memory version of the water maze task, but performed poorly in the working memory version of the water maze task and the object recognition memory task, relative to the control rats that received the i.c.v. infusion of Abeta(35-25) (inactive peptide) and saline treatment. By contrast, Abeta(25-35) rats with agmatine treatment did not show performance impairments in the working memory version of the water maze task and the object recognition memory task. In Experiment 2, Abeta(25-35) rats with saline treatment were significantly impaired in the standard radial arm maze task, but only displayed no or very mild impairments in the delayed non-match to position and reference memory versions of the radial arm maze task, T-maze, object recognition memory task, both the reference and working memory versions of the water maze task, elevated plus maze and open field. By contrast, Abeta(25-35) rats with agmatine treatment were not impaired in the standard radial arm maze and performed even better than the controls in the reference memory version of the task. These results demonstrate that agmatine is able to protect against Abeta(25-35)-induced memory deficits.
淀粉样β片段 25-35（Abeta(25-35)）是全长 Abeta(1-42)的神经毒性结构域，可导致啮齿动物的记忆损伤。最近的研究表明，胍丁胺，脱羧精氨酸，具有神经保护作用。本研究通过一系列行为测试，在 Abeta(25-35)（30 nmol）双侧侧脑室输注后的第 4-6 周（实验 1）和第 4-14 周（实验 2）期间进行了研究，并评估了胍丁胺（40 mg/kg）对 Abeta(25-35)的保护作用输注前 30 分钟腹腔内给药，连续 9 天每天一次。在实验 1 中，用生理盐水治疗的 Abeta(25-35)大鼠在高架十字迷宫和开阔场中未受损，在水迷宫任务的参考记忆版本中轻度受损，但在水迷宫任务的工作记忆版本和物体识别记忆任务中表现不佳，与接受 Abeta(35-25)（无活性肽）和生理盐水治疗的对照大鼠相比。相比之下，接受胍丁胺治疗的 Abeta(25-35)大鼠在水迷宫任务的工作记忆版本和物体识别记忆任务中未表现出行为损伤。在实验 2 中，用生理盐水治疗的 Abeta(25-35)大鼠在标准放射臂迷宫任务中明显受损，但仅在延迟非匹配位置和参考记忆版本的放射臂迷宫任务、T 迷宫、物体识别记忆任务、水迷宫任务的参考和工作记忆版本、高架十字迷宫和开阔场中表现出无或轻度损伤。相比之下，接受胍丁胺治疗的 Abeta(25-35)大鼠在标准放射臂迷宫任务中不受损伤，在任务的参考记忆版本中表现甚至优于对照组。这些结果表明，胍丁胺能够防止 Abeta(25-35)诱导的记忆缺陷。
