Chronic treatment with agmatine, similarly to fluoxetine, may cause antidepressant-like effects mediated, at least in part, by the modulation of hippocampal plasticity. However, the ability of chronic treatment with agmatine to cause antidepressant-like effects associated with the modulation of mammalian target of rapamycin (mTOR) signaling pathway and protection against neuronal death remains to be established. In this study, we investigated the effects of agmatine (0.1 mg/kg, p.o.) and the conventional antidepressant fluoxetine (10 mg/kg, p.o.) treatment on the levels of phosphorylated mTOR (p-mTOR), neuronal death, and overall volume in the hippocampal dentate gyrus (DG) of mice exposed to chronic corticosterone (20 mg/kg, p.o.) treatment for 21 days, a model of stress and depressive-like behavior. Chronic corticosterone treatment increased cell death in the sub-granular zone (SGZ) of the DG, as assessed by Fluoro-Jade B labeling. Agmatine, similarly to fluoxetine, was capable of reversing this alteration in the entire DG, an effect more evident in the ventral portion of the hippocampus. Additionally, reduced phosphorylation of mTOR (Ser²⁴⁴⁸), a pro-survival protein that is active when phosphorylated at Ser²⁴⁴⁸, was observed in the whole hippocampal DG in corticosterone-treated mice, an effect not observed in agmatine or fluoxetine-treated mice. Chronic exposure to corticosterone caused a significant reduction in overall hippocampal volume, although no alterations were observed between the groups with regards to DG volume. Altogether, the results indicate that agmatine, similar to fluoxetine, was able to counteract corticosterone-induced impairment on mTOR signaling and cell death in hippocampal DG.

中文翻译：

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胍丁胺对皮质酮诱导的损伤对海马mTOR信号转导和细胞死亡的保护作用。

与氟西汀类似，用胍丁胺进行的慢性治疗可引起抗抑郁样作用，至少部分地通过调节海马可塑性来介导。然而，用胍丁胺长期治疗引起与抗雷帕霉素（mTOR）信号转导通路的哺乳动物靶标的调节和抗神经元死亡相关的抗抑郁样作用的能力仍有待建立。在这项研究中，我们研究了胍丁胺（0.1 mg / kg，口服）和常规抗抑郁药氟西汀（10 mg / kg，口服）治疗对磷酸化mTOR（p-mTOR）水平，神经元死亡和总体积的影响。暴露于慢性皮质酮（20 mg / kg，po）治疗21天的海马齿状回（DG）小鼠中，这是一种应激和抑郁样行为的模型。慢性皮质酮治疗可增加DG颗粒下区域（SGZ）的细胞死亡，如Fluoro-Jade B标记所评估。类似于氟西汀的胍丁胺能够逆转整个DG中的这种改变，这种作用在海马腹侧部分更为明显。此外，mTOR（Ser²⁴⁴⁸）是一种在皮质酮治疗的小鼠的整个海马DG中观察到的在Ser ²⁴⁴⁸磷酸化时有活性的促存活蛋白，在胍丁胺或氟西汀治疗的小鼠中未观察到这种作用。长期暴露于皮质酮导致海马总体积显着减少，尽管两组之间的DG体积未见变化。总之，结果表明，类似于氟西汀的胍丁胺，能够抵消皮质酮诱导的海马DG mTOR信号转导和细胞死亡的损伤。