| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Yang, Chun Dong, Chao Yang, Jun Han, Mei Yao, Wei Ma, Min Morisseau, Christophe Ishima, Tamaki Zhang, Ji-chun Wagner, Karen M. Ren, Qian Hashimoto, Kenji Hammock, Bruce D. |
| Description |
Author Affiliation: Ren Q ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Ma M ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Ishima T ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Morisseau C ( Department of Entomology and Nematology, University of California Davis Comprehensive Cancer Center, University of California, Davis, CA 95616.); Yang J ( Department of Entomology and Nematology, University of California Davis Comprehensive Cancer Center, University of California, Davis, CA 95616.); Wagner KM ( Department of Entomology and Nematology, University of California Davis Comprehensive Cancer Center, University of California, Davis, CA 95616.); Zhang JC ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Yang C ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Yao W ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Dong C ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Han M ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); Hammock BD ( Department of Entomology and Nematology, University of California Davis Comprehensive Cancer Center, University of California, Davis, CA 95616 bdhammock@ucdavis.edu hashimoto@faculty.chiba-u.jp.); Hashimoto K ( Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan); |
| Abstract |
Depression is a severe and chronic psychiatric disease, affecting 350 million subjects worldwide. Although multiple antidepressants have been used in the treatment of depressive symptoms, their beneficial effects are limited. The soluble epoxide hydrolase (sEH) plays a key role in the inflammation that is involved in depression. Thus, we examined here the role of sEH in depression. In both inflammation and social defeat stress models of depression, a potent sEH inhibitor, TPPU, displayed rapid antidepressant effects. Expression of sEH protein in the brain from chronically stressed (susceptible) mice was higher than of control mice. Furthermore, expression of sEH protein in postmortem brain samples of patients with psychiatric diseases, including depression, bipolar disorder, and schizophrenia, was higher than controls. This finding suggests that increased sEH levels might be involved in the pathogenesis of certain psychiatric diseases. In support of this hypothesis, pretreatment with TPPU prevented the onset of depression-like behaviors after inflammation or repeated social defeat stress. Moreover, sEH KO mice did not show depression-like behavior after repeated social defeat stress, suggesting stress resilience. The sEH KO mice showed increased brain-derived neurotrophic factor (BDNF) and phosphorylation of its receptor TrkB in the prefrontal cortex, hippocampus, but not nucleus accumbens, suggesting that increased BDNF-TrkB signaling in the prefrontal cortex and hippocampus confer stress resilience. All of these findings suggest that sEH plays a key role in the pathophysiology of depression, and that epoxy fatty acids, their mimics, as well as sEH inhibitors could be potential therapeutic or prophylactic drugs for depression. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
13 |
| Volume Number |
113 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2016-04-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Depression Drug Therapy Epoxide Hydrolases Antagonists & Inhibitors Genetics Phenylurea Compounds Pharmacology Piperidines Stress, Psychological Animals Antidepressive Agents Brain Metabolism Brain-Derived Neurotrophic Factor Disease Models, Animal Enzyme Inhibitors Pharmacokinetics Inflammation Complications Mice, Inbred C57BL Mice, Knockout Oxylipins Rats, Mutant Strains Social Behavior Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
