ArticleProceedings of the National Academy of Sciences of the United States of America2016
Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.
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Who cites it
103 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- The Impact of Nutrition and Intestinal Microbiome on Elderly Depression-A Systematic Review.Nutrients · 2020Pooled it
- Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis.Molecular psychiatry · 2021Trial
- Soluble Epoxide Hydrolase Inhibition Regulates Septoclast Activity to Promote Long Bone Growth and Fracture Healing by Enhancing Endothelial-to-Mesenchymal Notch Signalling.Cell proliferation · 2026Article
- Epoxide Hydrolase Family: Biological Functions, Disease Mechanisms, and Emerging Therapeutic Strategies.Biology · 2026Review
- Compromised hepatic bilirubin clearance drives depressive symptoms via regulating microglial engulfment of dendritic spines.Journal of neuroinflammation · 2026Article
- The role of arachidonic acid metabolites in major depressive disorder: mechanisms and therapeutic implications.Metabolic brain disease · 2025Review
- EETs Reduction Contributes to Granulosa Cell Senescence and Endometriosis-Associated Infertility via the PI3K/AKT/mTOR Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The serum levels of polyunsaturated fatty acids contribute to the antidepressant-like effects of 18β-Glycyrrhetinic acid in mice.Psychopharmacology · 2025Article
- A cautionary tale: Non-steroidal anti-inflammatory drug use and localized provoked vulvodynia.The journal of pain · 2025Article
- Central-peripheral neuroimmune dynamics in psychological stress and depression: insights from current research.Molecular psychiatry · 2025Review
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Inhibition of Soluble Epoxide Hydrolase Prevents Docetaxel-Induced Painful Peripheral Neuropathy.International journal of molecular sciences · 2025Article
- Review
- Inhibition of soluble epoxide hydrolase confers neuroprotection and restores microglial homeostasis in a tauopathy mouse model.Molecular neurodegeneration · 2025Article
- The role of natural products and traditional Chinese medicine formulas in postpartum depression: mechanism and prospects.Frontiers in pharmacology · 2025Review
- A Naturalistic Prospective Study of the Prognostic Impact of EPHX2 in Major Depressive Disorder: Impulsivity may be an Important Factor.Depression and anxiety · 2025Observational
- Inhibiting the soluble epoxide hydrolase increases the EpFAs and ERK1/2 expression in the hippocampus of LiCl-pilocarpine post-status epilepticus rat model.IBRO neuroscience reports · 2024Article
- Effect of Shenqi Jieyu formula on inflammatory response pathway in hippocampus of postpartum depression rats.Heliyon · 2024Article
- Inhibition of soluble epoxide hydrolase enhances the dentin-pulp complex regeneration mediated by crosstalk between vascular endothelial cells and dental pulp stem cells.Journal of translational medicine · 2024Article
- A resource of induced pluripotent stem cell (iPSC) lines including clinical, genomic, and cellular data from genetically isolated families with mood and psychotic disorders.Translational psychiatry · 2023Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.