title: Zinc and imipramine reverse the depression-like behavior in mice induced by chronic restraint stress.
abstract: 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.
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Mo
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China. Electronic address: huangjlsmmu@126.com.
authors.forename: Junlong
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Naval Hygiene, Second Military Medical University, Shanghai, China. Electronic address: shenhuicn@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012149:Restraint, Physical / Q000523:psychology*; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000209:etiology / Q000523:psychology*; D015032:Zinc / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C495797:GPR39 protein, human; D043562:Receptors, G-Protein-Coupled; D016194:Receptors, N-Methyl-D-Aspartate; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D015032:Zinc; D007099:Imipramine; D003345:Corticosterone
keywords: Chronic restraint stress; Depression; GPR39; Imipramine; Zinc