Bruce D. Hammock, Ph.D.
University of California, Davis
An NIEHS grantee and colleagues discovered that a chemical inhibitor of the soluble epoxide hydrolase (sEH) enzyme may be a new tool to treat depression. The enzyme plays a key role in inflammation, which is involved in depression. Researchers found that the sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl) urea (TPPU), displayed rapid antidepressant effects in mice.
Researchers observed mice for depression-like behavior after repeated social stress. They found that administering TPPU reduced depression-like behaviors. Inhibiting sEH in the mice also produced resilience to the repeated stress.
The researchers also observed higher levels of sEH expression in key brain regions of the chronically stressed mice than in mice not subject to repeated stress. They then examined postmortem human brain samples from patients with psychiatric diseases, including depression, and found that these brains expressed higher levels of sEH than brain samples from people with no psychiatric diagnoses.
Depression, the most common and debilitating psychiatric disorder, affects 350 million people around the world. This study improves the understanding of mechanisms involved in depression by showing that sEH is involved in its development. As a result, sEH inhibitors have potential as effective therapeutic drugs for depression.
Citation: Ren Q, Ma M, Ishima T, Morisseau C, Yang J, Wagner KM, Zhang JC, Yang C, Yao W, Dong C, Han M, Hammock BD, Hashimoto K. 2016. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc Natl Acad Sci U S A 113(13):E1944-E1952.