Possible Involvement of N-methyl-D-aspartate Receptor (NMDA-R) in the Antidepressant-like Effect of Trigonelline in Male Mice
Possible Involvement of N-methyl-D-aspartate Receptor (NMDA-R) in the Antidepressant-like Effect of Trigonelline in Male Mice
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DOI：
10.2174/1381612826666200610181259
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发表时间：
2020-01-01
影响因子：
3.1
通讯作者：
Amini-Khoei, Hossein
中科院分区：
文献类型：
--
作者：
Anjomshoa, Maryam;Boroujeni, Shakiba N.;Amini-Khoei, Hossein
背景和目的：抑郁症是一种全球患病率较高的情绪障碍。抑郁症与海马体积的减少及其神经递质功能的变化有关。葫芦巴碱是一种具有神经保护活性的生物碱。本研究的目的是考虑海马的组织病理学改变，探讨 N-甲基-天冬氨酸 (NMDA) 受体在葫芦巴碱抗抑郁样作用中的可能作用。方法：将60只海军医学研究所（NMRI）雄性小鼠分为6组，第1组（生理盐水），第2组、第3组和第4组（葫芦巴碱10、50和100 mg/kg剂量），第5组（有效剂量葫芦巴碱+NMDA激动剂）和第6组（亚有效剂量葫芦巴碱+NMDA拮抗剂）。强迫游泳测试（FST）用于评估抑郁样行为。在深度麻醉下分离海马并用于组织病理学评估以及NMDA受体基因表达评估。结果：与对照组相比，10、50 和 100 剂量的葫芦巴碱显着缩短了 FST 中的不动时间。给予亚有效剂量的葫芦巴碱加氯胺酮（一种NMDA受体拮抗剂）可增强亚有效剂量的葫芦巴碱的作用。此外，有效剂量的葫芦巴碱与NMDA共同治疗减轻了葫芦巴碱的抗抑郁样作用。 50 和 100 mg/kg 剂量的葫芦巴碱显着增加了海马 CA1 区域的直径。结论：葫芦巴碱在小鼠体内表现出抗抑郁样作用，可能是通过减弱 NMDA 受体活性和增加海马 CA1 区的活性来实现的。
Background and Aim: Depression is a mood disorder with high global prevalence. Depression is associated with a reduction in the hippocampal volume and change in its neurotransmitters function. Trigonelline is an alkaloid with neuroprotective activity. The aim of this study was to investigate the possible role of N-methyl-Daspartate (NMDA) receptor in the antidepressant-like effect of trigonelline, considering histopathological modifications of the hippocampus. Methods: 60 Naval Medical Research Institute (NMRI) male mice were divided into 6 groups including group 1 (normal saline), groups 2, 3 and 4 (trigonelline at doses of 10, 50 and 100 mg/kg), group 5 (effective dose of trigonelline plus NMDA agonist) and group 6 (sub-effective dose of trigonelline plus NMDA antagonist). Forced swimming test ( FST) was used to assess depressive-like behavior. Hippocampi were separated under deep anesthesia and used for histopathological evaluation as well as NMDA receptor gene expression assessment. Results: Trigonelline at doses of 10, 50 and 100 significantly reduced the immobility time in the FST in comparison to the control group. The administration of the sub-effective dose of trigonelline plus ketamine (an NMDA receptor antagonist) potentiated the effect of the sub-effective dose of trigonelline. In addition, co-treatment of an effective dose of trigonelline with NMDA mitigated the antidepressant-like effect of trigonelline. Trigonelline at doses of 50 and 100 mg/kg significantly increased the diameter of the CA1 area of the hippocampus. Conclusion: Trigonelline showed an antidepressant-like effect in mice, probably via attenuation of NMDA receptor activity and an increase in the CA1 region of the hippocampus.