Differential proteomic analysis of the anti-depressive effects of oleamide in a rat chronic mild stress model of depression
Autor: | Rong Zhang, Jing Shen, Fang Wang, Lin Ge, Jingyu Yang, Zhang Jinghai, Chunfu Wu, Ming-ming Zhu, Hui-Fang Tian |
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Rok vydání: | 2014 |
Předmět: |
Male
Proteomics medicine.medical_specialty Oleamide Protein subunit Clinical Biochemistry Neuropeptide Adenylate kinase Nerve Tissue Proteins Oleic Acids Biology Toxicology Biochemistry Hippocampus GSTA4 Rats Sprague-Dawley Behavioral Neuroscience chemistry.chemical_compound Internal medicine Biogenic amine Fluoxetine medicine Initiation factor Animals Electrophoresis Gel Two-Dimensional Biological Psychiatry Pharmacology chemistry.chemical_classification Depression Glutathione Antidepressive Agents Rats Disease Models Animal Endocrinology chemistry Biomarkers Selective Serotonin Reuptake Inhibitors Stress Psychological |
Zdroj: | Pharmacology, biochemistry, and behavior. 131 |
ISSN: | 1873-5177 |
Popis: | 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. |
Databáze: | OpenAIRE |
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