The Role of Liver Soluble Epoxide Hydrolase in Modulating the Impact of Chronic Stress on Depression and Alzheimer's Disease Pathogenesis in Mice

The link between depression and Alzheimer's disease (AD) is increasingly recognized, yet the underlying molecular mechanisms remain poorly understood. Chronic stress is known to contribute to both depression and AD. The Ephx2 gene encodes soluble epoxide hydrolase (sEH), an enzyme that regulates 14,15-EET, a signaling molecule that may influence both AD pathogenesis and depressive symptoms. This research makes use of a mouse model to explore the influence of 14,15-EET on signaling pathways that are linked with depression and Alzheimer's disease (AD), with attention given to its involvement in amyloid-beta (A) buildup and tau protein hyperphosphorylation. The study is centered on analyzing the liver sEH's part in altering how chronic stress impacts depressive behavior patterns and AD-related pathology. In the experiment, adult C57BL/6J mice, which included wild-type, sEH knockout (sEH^-/-), and those treated with an sEH inhibitor, were subjected to chronic stress and AD induction to evaluate these influences.