Zinc and imipramine reverse the depression-like behavior in mice induced by chronic restraint stress
Zinc and imipramine reverse the depression-like behavior in mice induced by chronic restraint stress
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锌和丙咪嗪逆转慢性束缚应激引起的小鼠抑郁样行为
DOI：
10.1016/j.jad.2016.03.017
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发表时间：
2016-06-01
影响因子：
6.6
通讯作者：
Shen, Hui
中科院分区：
文献类型：
--
作者：
Ding, Qin;Li, Hongxia;Shen, Hui
抑郁症是一种常见的精神病理障碍。对抑郁症的研究表明，锌在抑郁症的病理生理和治疗中起着重要作用。在本研究中，我们观察了锌和丙咪嗪单独或联合补充锌和丙咪嗪对慢性约束应激（CRS）小鼠的影响。此外，还探讨了锌受体（G蛋白偶联受体39，GPR39）相关途径可能发挥的作用。CRS暴露3周后，观察到体重下降和皮质酮（CORT）升高。结果表明，CRS可引起大鼠血清锌含量降低，海马锌含量升高，尾悬试验中静止时间延长，自发活动试验中运动距离缩短，而CRS暴露后3周，单独补充锌（30 mg/kg）和丙咪嗪（20 mg/kg）以及锌（15 mg/kg）和丙咪嗪（5 mg/kg）可使其恢复正常。此外，GPR39、camp反应元件结合蛋白（CREB）、脑源性神经营养因子（BDNF）和n-甲基-d -天冬氨酸受体（NMDAR） mRNA表达的变化可以通过上述处理逆转。上述结果表明，本研究观察到的CRS暴露动物血清和海马锌代谢失调及抑郁样行为可以通过锌和丙咪嗪恢复正常。低剂量锌与丙咪嗪联用有协同作用。其机制可能与GPR39受体相关通路有关。(c) 2016 Elsevier B.V.版权所有
Depression is a common psychopathological disorders. Studies of depression have indicated that zinc play a role in the depression pathophysiology and treatment. In present study, we examined the effects of zinc and imipramine supplement alone or combination of zinc and imipramine in mice induced by chronic restraint stress (CRS). Moreover, the possible roles of zinc receptor (G protein-coupled receptor 39, GPR39)-related pathway was investigated. Decreased weight and increased corticosterone (CORT) were observed after 3 weeks CRS exposure. It was shown that CRS induced lower serum zinc, higher hippocampal zinc, increased immobility time in tail suspension test and decreased movement distance in spontaneous activity test, which could be normalized by zinc (30 mg/kg) and imipramine (20 mg/kg) supplement alone and combination of zinc (15 mg/kg) and imipramine (5 mg/kg) for 3 weeks after CRS exposure. Moreover, the changes in mRNA expressions of GPR39, cAMP-response element binding protein (CREB), brain-derived neurotropic factor (BDNF) and n-methytl-D-aspartate receptors (NMDAR) could be reversed by the same treatment mentioned above. These results suggested that zinc dyshomeostasis in serum and hippocampus and depression-like behavior in CRS exposure animals observed in present study could be normalized by zinc and imipramine. The combination of zinc and imipramine in low dose has synergetic effects. The possible mechanism might be correlated to GPR39 receptor-related pathway. (c) 2016 Elsevier B.V. All rights reserved.