Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Department of Analytical Chemistry, Faculty of Chemistry, Jagiellonian University, Krakow, Poland.
Int J Neuropsychopharmacol. 2014 Mar;17(3):393-405. doi: 10.1017/S1461145713001089. Epub 2013 Sep 26.
Recent data suggests that the glutamatergic system is involved in the pathophysiology and treatment of major depressive disorder (MDD) and that the N-methyl-D-aspartate (NMDA) receptor is a potential target for antidepressant drugs. The magnesium ion blocks the ion channel of the NMDA receptor and prevents its excessive activation. Some preclinical and clinical evidence suggests also that magnesium may be useful in the treatment of depression. The present study investigated the effect of magnesium treatment (10, 15 and 20 mg/kg, given as magnesium hydroaspartate) in the chronic mild stress (CMS) model of depression in rats. Moreover, the effect of CMS and magnesium (with an effective dose) on the level of the proteins related to the glutamatergic system (GluN1, GluN2A, GluN2B and PSD-95) in the hippocampus, prefrontal cortex (PFC) and amygdala were examined. A significant reduction in the sucrose intake induced by CMS was increased by magnesium treatment at a dose of 15 mg/kg, beginning from the third week of administration. Magnesium did not affect this behavioural parameter in the control animals. CMS significantly increased the level of the GluN1 subunit in the amygdala (by 174%) and GluN2A in the hippocampus (by 191%), both of which were significantly attenuated by magnesium treatment. Moreover, magnesium treatment in CMS animals increased the level of GluN2B (by 116%) and PSD-95 (by 150%) in the PFC. The present results for the first time demonstrate the antidepressant-like activity of magnesium in the animal model of anhedonia (CMS), thus indicating the possible involvement of the NMDA/glutamatergic receptors in this activity.
最近的数据表明，谷氨酸能系统参与了重性抑郁障碍（MDD）的病理生理学和治疗，而 N-甲基-D-天冬氨酸（NMDA）受体是抗抑郁药物的潜在靶点。镁离子阻断 NMDA 受体的离子通道，防止其过度激活。一些临床前和临床证据表明，镁可能对治疗抑郁症有用。本研究调查了镁治疗（10、15 和 20mg/kg，给予镁天冬氨酸）对慢性轻度应激（CMS）大鼠抑郁模型的影响。此外，还研究了 CMS 和镁（有效剂量）对海马、前额叶皮层（PFC）和杏仁核中与谷氨酸能系统相关的蛋白质水平（GluN1、GluN2A、GluN2B 和 PSD-95）的影响。CMS 导致的蔗糖摄入量显著减少，在给予镁 15mg/kg 的第 3 周开始增加。镁对对照组动物的这种行为参数没有影响。CMS 显著增加了杏仁核中 GluN1 亚基（增加 174%）和海马中 GluN2A（增加 191%）的水平，镁治疗显著减弱了这两种水平的增加。此外，镁治疗还增加了 CMS 动物 PFC 中 GluN2B（增加 116%）和 PSD-95（增加 150%）的水平。本研究结果首次证明了镁在快感缺失动物模型（CMS）中的抗抑郁样活性，表明 NMDA/谷氨酸能受体可能参与了这种活性。
