Zhu Meng-Yang, Wang Wei-Ping, Cai Zheng-Wei, Regunathan Soundar, Ordway Gregory
Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37604, USA.
Eur J Neurosci. 2008 Mar;27(6):1320-32. doi: 10.1111/j.1460-9568.2008.06104.x.
Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with beta-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress.
胍丁胺是一种由精氨酸脱羧酶催化精氨酸脱羧产生的内源性胺。胍丁胺被认为是一种新型神经调质，在中枢神经系统中具有神经保护特性。本研究检测了胍丁胺是否对重复束缚应激诱导的大鼠内侧前额叶皮质和海马体形态变化具有神经保护作用。将Sprague-Dawley大鼠每天进行6小时的束缚应激，持续21天。用β-微管蛋白III进行免疫组织化学染色显示，重复束缚应激导致内侧前额叶皮质和海马体出现明显的形态改变。同时给予胍丁胺（50毫克/千克/天，腹腔注射）可预防应激诱导的改变。有趣的是，通过高效液相色谱法测定，与对照组相比，重复束缚大鼠的前额叶皮质、海马体以及纹状体和下丘脑的内源性胍丁胺水平显著降低。重复束缚动物内源性胍丁胺水平降低的同时，相同区域的精氨酸脱羧酶蛋白水平显著升高。此外，给束缚大鼠注射外源性胍丁胺可消除精氨酸脱羧酶蛋白水平升高的现象。综上所述，这些结果表明，外源性给予胍丁胺对重复束缚诱导的内侧前额叶皮质和海马体结构变化具有神经保护作用。这些发现表明，应激诱导的大鼠脑内源性胍丁胺水平降低可能在重复束缚应激诱导的神经元病理过程中起促进作用。
