title: Differential proteomic analysis of the anti-depressive effects of oleamide in a rat chronic mild stress model of depression.
abstract: Depression is a complex psychiatric disorder, and its etiology and pathophysiology are not completely understood. Depression involves changes in many biogenic amine, neuropeptide, and oxidative systems, as well as alterations in neuroendocrine function and immune-inflammatory pathways. Oleamide is a fatty amide which exhibits pharmacological effects leading to hypnosis, sedation, and anti-anxiety effects. In the present study, the chronic mild stress (CMS) model was used to investigate the antidepressant-like activity of oleamide. Rats were exposed to 10weeks of CMS or control conditions and were then subsequently treated with 2weeks of daily oleamide (5mg/kg, i.p.), fluoxetine (10mg/kg, i.p.), or vehicle. Protein extracts from the hippocampus were then collected, and hippocampal maps were generated by way of two-dimensional gel electrophoresis (2-DE). Altered proteins induced by CMS and oleamide were identified through mass spectrometry and database searches. Compared to the control group, the CMS rats exhibited significantly less body weight gain and decreased sucrose consumption. Treatment with oleamide caused a reversal of the CMS-induced deficit in sucrose consumption. In the proteomic analysis, 12 protein spots were selected and identified. CMS increased the levels of adenylate kinase isoenzyme 1 (AK1), nucleoside diphosphate kinase B (NDKB), histidine triad nucleotide-binding protein 1 (HINT1), acyl-protein thioesterase 2 (APT-2), and glutathione S-transferase A4 (GSTA4). Compared to the CMS samples, seven spots changed significantly following treatment with oleamide, including GSTA4, glutathione S-transferase A6 (GSTA6), GTP-binding nuclear protein Ran (Ran-GTP), ATP synthase subunit d, transgelin-3, small ubiquitin-related modifier 2 (SUMO2), and eukaryotic translation initiation factor 5A-1 (eIF5A1). Of these seven proteins, the level of eIF5A1 was up-regulated, whereas the remaining proteins were down-regulated. In conclusion, oleamide has antidepressant-like properties in the CMS rat model. The identification of proteins altered by CMS and oleamide treatment provides support for targeting these proteins in the development of novel therapies for depression.
authors: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Lin
authors: L
authors: Ge
authors: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Ming-Ming
authors: MM
authors: Zhu
authors: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Jing-Yu
authors: JY
authors: Yang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Fang
authors: F
authors: Wang
authors: School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Rong
authors: R
authors: Zhang
authors: School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Jing-Hai
authors: JH
authors: Zhang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Central Laboratory, Beijing Cancer Hospital & Institute, Beijing 100142, PR China.
authors: Jing
authors: J
authors: Shen
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Central Laboratory, Beijing Cancer Hospital & Institute, Beijing 100142, PR China.
authors: Hui-Fang
authors: HF
authors: Tian
authors: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: chunfuw@gmail.com.
authors: Chun-Fu
authors: CF
authors: Wu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009829:Oleic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy*
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D005473:Fluoxetine; D009419:Nerve Tissue Proteins; D009829:Oleic Acids; D017367:Selective Serotonin Reuptake Inhibitors; C029407:oleylamide
keywords: Chronic mild stress; Hippocampus; Oleamide; Proteomics