Background and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area of the hippocampus. Methods. Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups () (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. Results. Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. Conclusion. Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.

中文翻译：

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芦丁通过增加海马 CA3 直径在母体分离应激小鼠模型中发挥抗抑郁样作用：可能涉及 NMDA 受体。

背景和目的。芦丁是一种具有神经保护活性的黄酮醇。本研究的目的是研究谷氨酸能系统在母体分离 (MS) 应激小鼠模型中芦丁的抗抑郁样作用中的作用，重点是海马 CA3 区域的组织学变化。方法。从出生后第 2 天 (PND) 到第 14 天，每天 3 小时将小鼠新生儿暴露于 MS 模式。对照和 MS 小鼠分别分为 16 组 (）（每组8组）包括接受生理盐水的小鼠，接受10、50和100 mg/kg剂量芦丁的小鼠，接受150 mg/kg剂量NMDA的小鼠，接受氯胺酮的小鼠（ NMDA 拮抗剂）以 0.25 mg/kg 的剂量，接受 NMDA 拮抗剂加上亚有效剂量的芦丁的小鼠，以及接受 NMDA 加上有效剂量的芦丁的小鼠。进行强迫游泳试验（FST）。之后，在组织病理学变化的情况下评估海马体以及 NR2A 和 NR2B 基因的表达。结果. 芦丁显着减少了 FST 中的不动时间。MS小鼠NMDA受体NR2A和NR2B亚基的表达明显高于对照组。芦丁显着降低海马中 NR2B 和 NR2A 亚基的表达。MS小鼠海马CA3直径和暗神经元百分比分别显着降低和增加，在芦丁给药后部分逆转。结论。芦丁部分地通过对海马的神经保护作用发挥抗抑郁样作用。我们得出结论，NMDA 受体至少部分地介导了芦丁的有益作用。