Agmatine, an endogenous amine derived from decarboxylation of L-arginine catalyzed by arginine decarboxylase, has been proposed as a neurotransmitter or neuromodulator in the brain. In the present study, we examined whether agmatine has neuroprotective effects against repeated immobilization-induced morphological changes in brain tissues and possible effects of immobilization stress on endogenous agmatine levels and arginine decarboxylase expression in rat brains. Sprague-Dawley rats were subjected to 2h immobilization stress daily for 7 days. This paradigm significantly increased plasma corticosterone levels, and the glutamate efflux in the hippocampus as measured by in vivo microdialysis. Immunohistochemical staining with beta-tubulin III showed that repeated immobilization caused marked morphological alterations in the hippocampus and medial prefrontal cortex that were prevented by simultaneous treatment with agmatine (50mg/kg/day), i.p.). Likewise, endogenous agmatine levels measured by high-performance liquid chromatography in the prefrontal cortex, hippocampus, striatum and hypothalamus were significantly increased by immobilization, as compared to controls. The increased endogenous agmatine levels, ranging from 92 to 265% of controls, were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. These results demonstrate that the administration of exogenous agmatine protects the hippocampus and medial prefrontal cortex against neuronal insults caused by repeated immobilization. The parallel increase in endogenous brain agmatine and arginine decarboxylase protein levels triggered by repeated immobilization indicates that the endogenous agmatine system may play an important role in adaptation to stress as a potential neuronal self-protection mechanism.

译文

Agmatine是一种内源性胺,由精氨酸脱羧酶催化的L-精氨酸脱羧衍生而来,已被提议作为大脑中的神经递质或神经调节剂。在本研究中,我们检查了agmatine是否对反复固定诱导的脑组织形态学变化具有神经保护作用,以及固定应激对大鼠脑中内源性agmatine水平和精氨酸脱羧酶表达的可能影响。Sprague-Dawley大鼠每天进行2小时的固定应激7天。通过体内微透析测量,这种范例显着增加了血浆皮质酮水平和海马中的谷氨酸外排。用 β-微管蛋白III进行的免疫组织化学染色显示,反复固定会导致海马和内侧前额叶皮层发生明显的形态学改变,而同时用agmatine (50 mg/kg/天) 进行治疗则可以防止这种改变。同样,与对照组相比,通过固定,通过高效液相色谱法测量的前额叶皮层,海马,纹状体和下丘脑中的内源性agmatine水平显着增加。增加的内源性苯丙胺水平 (从92到265% 的对照范围) 伴随着相同区域中精氨酸脱羧酶蛋白水平的显着增加。这些结果表明,外源性agmatine的给药可保护海马和内侧前额叶皮层免受反复固定引起的神经元损伤。反复固定化引发的内源性脑agmatine和精氨酸脱羧酶蛋白水平平行升高,表明内源性agmatine系统可能作为一种潜在的神经元自我保护机制在适应压力方面发挥重要作用。

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