Department of Anatomy, Brain Health Research Centre, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand.
Neuroscience. 2012 Dec 13;226:178-96. doi: 10.1016/j.neuroscience.2012.09.013. Epub 2012 Sep 16.
A growing body of evidence suggests the involvement of L-arginine and its metabolites in the ageing and neurodegenerative processes. The present study assessed behavioural performance in 4- (young), 12- (middle-aged) and 24- (aged) month-old male Sprague-Dawley rats, and investigated age-related changes in the activity of two key arginine metabolic enzymes, nitric oxide synthase (NOS) and arginase, and the levels of L-arginine and its downstream metabolites in a number of memory-related brain structures. Aged rats were less anxious and performed poorly in the water maze task relative to the young and middle-aged rats, and both middle-aged and aged rats displayed reduced exploratory activity relative to the young ones. There were significant age-related changes in NOS and arginase activities, and the levels of L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine and glutamate, but not γ-aminobutyric acid, in the CA1, CA2/3 and dentate gyrus sub-regions of the hippocampus and the prefrontal, entorhinal, perirhinal, postrhinal and temporal (an auditory cortex) cortices in a region-specific manner. Cluster analyses revealed that the nine related neurochemical variables formed distinct groups, which changed as a function of ageing. Multiple regression analyses revealed a number of significant correlations between the neurochemical and behavioural variables. The present study further supports the involvement of arginine metabolism in the ageing process, and provides further evidence of the effects of animals' behavioural experience on arginine metabolism.
越来越多的证据表明，L-精氨酸及其代谢物参与了衰老和神经退行性过程。本研究评估了 4 个月（年轻）、12 个月（中年）和 24 个月（老年）雄性 Sprague-Dawley 大鼠的行为表现，并研究了两种关键精氨酸代谢酶（一氧化氮合酶（NOS）和精氨酸酶）的活性以及与记忆相关的大脑结构中 L-精氨酸及其下游代谢物水平的年龄相关性变化。与年轻和中年大鼠相比，老年大鼠在水迷宫任务中表现出较少的焦虑和较差的表现，而中年和老年大鼠的探索性活动均低于年轻大鼠。NOS 和精氨酸酶活性以及 L-精氨酸、L-瓜氨酸、L-鸟氨酸、胍丁胺、腐胺、亚精胺、精胺和谷氨酸的水平在海马 CA1、CA2/3 和齿状回区以及前额叶、内嗅皮质、边缘皮质、后边缘皮质和颞叶（听觉皮质）区均有显著的年龄相关性变化，但γ-氨基丁酸除外。以区域特异性方式。聚类分析显示，这 9 个相关神经化学变量形成了不同的组，这些组随着年龄的变化而变化。多元回归分析显示，神经化学和行为变量之间存在许多显著相关性。本研究进一步支持了精氨酸代谢在衰老过程中的参与，并提供了动物行为经验对精氨酸代谢影响的进一步证据。
