title: Venlafaxine increases cell proliferation and regulates DISC1, PDE4B and NMDA receptor 2B expression in the hippocampus in chronic mild stress mice.
abstract: Recent evidence has identified disrupted in schizophrenia-1 (DISC1) as an important genetic risk factor for the development of many psychiatric disorders, including major depressive disorders. In addition, studies using animal models have demonstrated that chronic stress affects hippocampal structure and function. However, the functional effects of chronic stress on DISC1 remain unknown. Using a chronic mild stress (CMS) paradigm, we investigated the effects of CMS on depressive-like behaviors, hippocampal cell proliferation, and hippocampal protein expression of DISC1, phosphodiesterase 4B (PDE4B) and N-methyl-d-aspartate receptor 2B subunit (NMDA receptor 2B), which may be involved in the regulation of DISC1 and neurogenesis. We also examined the effects and possible mechanisms of the antidepressant venlafaxine in CMS mice. CMS increased the expression of DISC1 and PDE4B. Chronic treatment with venlafaxine blocked the increases in these proteins, and also reversed the CMS-induced decrease in neurogenesis and NMDA receptor 2B protein in the hippocampus. These results suggest that DISC1 may play an important role in the etiology of depression and in the action of antidepressants.
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China. Electronic address: xbli@mail.cmu.edu.cn.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yun
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D003863:Depression / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; C498794:Disc1 protein, mouse; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D000069470:Venlafaxine Hydrochloride; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C543000:PDE4B protein, mouse
keywords: Chronic mild stress; DISC1; Hippocampus; Neurogenesis; Venlafaxine