Department of Anatomy, University of Otago, New Zealand; Brain Health Research Centre, University of Otago, New Zealand.
Neuroscience. 2013 Mar 27;234:116-24. doi: 10.1016/j.neuroscience.2013.01.004. Epub 2013 Jan 11.
Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats.
越来越多的证据表明，精氨酸代谢的改变导致衰老过程中的认知能力下降。胍丁胺是精氨酸脱羧产物，具有多种药理学作用，包括调节行为功能。最近的一项研究表明，短期胍丁胺治疗可改善老年大鼠的认知功能。本研究旨在探讨腹腔内给予胍丁胺（40mg/kg，每日 1 次）4-6 周对老年 Sprague-Dawley 大鼠行为功能和神经化学的影响。与年轻大鼠相比，用生理盐水处理的老年大鼠在旷场中表现出明显减少的探索性活动，在水迷宫和物体识别记忆测试中空间学习和记忆受损。长期胍丁胺治疗可改善动物在水迷宫逆转测试和物体识别记忆测试中的表现，并显著抑制海马齿状回和前额叶皮质中与年龄相关的一氧化氮合酶活性升高。然而，这种长期补充并不能改善老年大鼠的探索性活动和空间参考学习及记忆。这些发现进一步表明，外源性胍丁胺选择性改善老年大鼠的行为功能。
