Rapid antidepressant actions of imipramine potentiated by zinc through PKA-dependented regulation of mTOR and CREB signaling

被引:8
作者
Huang, Yeqing [1 ]
Xu, Danhong [1 ]
Xiang, Haiqing [1 ]
Yan, Shi [2 ]
Sun, Fangfang [2 ]
Wei, Zhisheng [1 ]
机构
[1] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Sch Clin Med, Dept Neurol, 19 Nonglinxia Rd, Guangzhou 510080, Peoples R China
[2] Guangzhou Med Univ, Affiliated Hosp 2, Inst Neurosci, 250 Changgang East Rd, Guangzhou 510260, Peoples R China
关键词
Zinc; Imipramine; Depression; cAMP-response element binding protein; Mammalian target of rapamycin; Protein kinase A; KETAMINE; DEPRESSION; PATHWAY; BDNF; MODULATION; MECHANISMS; MODEL;
D O I
10.1016/j.bbrc.2019.08.059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The slow onset of traditional antidepressants has become an urgent clinical issue, researchers are constantly exploring new antidepressants with prompt action. Previous studies have found that zinc levels were decreased in serum and brain of depressed patients or animal models. Zinc treatment can improve depressive symptoms and enhance the antidepressant effects of monoamine antidepressants. However, its mechanism of action is still unclear. This present study aims to investigate whether the zinc can enhance the rapid action of traditional antidepressant imipramine and to explore the potential mechanisms of action through the rapid antidepressant targets CREB (cAMP-response element binding protein) and mTOR (mammalian target of the rapamycin). Drug treatment included intraperitoneal injection of imipramine or zinc alone and imipramine plus zinc. Zinc had a rapid enhanced antidepressive effect on the imipramine and achieved a rapid antidepressant effect similar to ketamine. Combination of zinc with imipramine rapidly enhanced the phosphorylation of mTOR Ser2448 and CREB Ser133, and increased the expression of mTOR and CREB, which were dependent on the activation of PIGS. In conclusion, combination therapy with zinc and monoamine antidepressants may overcome the problem of slow-onset action of traditional antidepressants in clinical uses. (C) 2019 Elsevier Inc. All rights reserved.
引用
收藏
页码:337 / 343
页数:7
相关论文
共 29 条
[1]   The phosphoinositide 3-kinase pathway and glycogen synthase kinase-3 positively regulate the activity of metal-responsive transcription factor-1 in response to zinc ions [J].
Andeol, Yannick ;
Bonneau, Jessica ;
Gagne, Laurence M. ;
Jacquet, Kevin ;
Rivest, Veronique ;
Huot, Marc-Etienne ;
Seguin, Carl .
BIOCHEMISTRY AND CELL BIOLOGY, 2018, 96 (06) :726-733
[2]   Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants [J].
Browne, Caroline A. ;
Lucki, Irwin .
FRONTIERS IN PHARMACOLOGY, 2013, 4
[3]   (2R,6R)-hydroxynorketamine rescues chronic stress-induced depression-like behavior through its actions in the midbrain periaqueductal gray [J].
Chou, Dylan ;
Peng, Hsien-Yu ;
Lin, Tzer-Bin ;
Lai, Cheng-Yuan ;
Hsieh, Ming-Chun ;
Wen, Yang-Cheng ;
Lee, An-Sheng ;
Wang, Hsueh-Hsiao ;
Yang, Po-Sheng ;
Chen, Gin-Den ;
Ho, Yu-Cheng .
NEUROPHARMACOLOGY, 2018, 139 :1-12
[4]   Zinc and imipramine reverse the depression-like behavior in mice induced by chronic restraint stress [J].
Ding, Qin ;
Li, Hongxia ;
Tian, Xue ;
Shen, Zhilei ;
Wang, Xiaoli ;
Mo, Fengfeng ;
Huang, Junlong ;
Shen, Hui .
JOURNAL OF AFFECTIVE DISORDERS, 2016, 197 :100-106
[5]   Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder [J].
Duncan, Wallace C., Jr. ;
Sarasso, Simone ;
Ferrarelli, Fabio ;
Selter, Jessica ;
Riedner, Brady A. ;
Hejazi, Nadia S. ;
Yuan, Peixiong ;
Brutsche, Nancy ;
Manji, Husseini K. ;
Tononi, Giulio ;
Zarate, Carlos A., Jr. .
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2013, 16 (02) :301-311
[6]   Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus [J].
Garcia, Leda S. B. ;
Comim, Clarissa M. ;
Valvassori, Samira S. ;
Reus, Gislaine Z. ;
Barbosa, Luciana M. ;
Andreazza, Ana Cristina ;
Stertz, Laura ;
Fries, Gabriel R. ;
Gavioli, Elaine Cristina ;
Kapczinski, Flavio ;
Quevedo, Joao .
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2008, 32 (01) :140-144
[7]  
Greden JF, 2002, J CLIN PSYCHIAT, V63, P3
[8]   Remodeling of Hippocampal Spine Synapses in the Rat Learned Helplessness Model of Depression [J].
Hajszan, Tibor ;
Dow, Antonia ;
Warner-Schmidt, Jennifer L. ;
Szigeti-Buck, Klara ;
Sallam, Nermin L. ;
Parducz, Arpad ;
Leranth, Csaba ;
Duman, Ronald S. .
BIOLOGICAL PSYCHIATRY, 2009, 65 (05) :392-400
[9]   Degradation of CREB-binding protein and modulation of type I interferon induction by the zinc finger motif of the porcine reproductive and respiratory syndrome virus nsp1α subunit [J].
Han, Mingyuan ;
Du, Yijun ;
Song, Cheng ;
Yoo, Dongwan .
VIRUS RESEARCH, 2013, 172 (1-2) :54-65
[10]   Periaqueductal Gray Glutamatergic Transmission Governs Chronic Stress-Induced Depression [J].
Ho, Yu-Cheng ;
Lin, Tzer-Bin ;
Hsieh, Ming-Chun ;
Lai, Cheng-Yuan ;
Chou, Dylan ;
Chau, Yat-Pang ;
Chen, Gin-Den ;
Peng, Hsien-Yu .
NEUROPSYCHOPHARMACOLOGY, 2018, 43 (02) :302-312