Lenti-hEPHX2 was used to overexpress the human EPHX2 gene, AAV-Ephx2-shRNAs was used to selectively decrease the expression of EPHX2 gene, pEf1a-Ephx2 plasmid DNA and a control plasmid (pEf1a-eYFP) (From
BrainVTA) were used to further characterize the effects of the overexpression of sEH.
The products used in this article from BrainVTA are in the table below
|
Control |
PT-0098 AAV2/8-Ef1a -eYFP -WPRE |
|
Custom-Made AAV |
AAV2/8-Ef1a-eYFP-P2A-Ephx2-WPREs |
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Recombinant DNA |
pEf1a-eYFP |
Pub Date: 2019-12-03,
DOI: 10.1016/j.celrep.2019.11.006 Email: [email protected]
Xi-He Qin, Zhou Wu, Jing-Hua Dong, Yuan-Ning Zeng, Wen-Chao Xiong, Ce Liu, Meng-Yao Wang, Min-Zhen Zhu, Wen-Jun Chen, Yuan Zhang, Qi-Yuan Huang and Xin-Hong Zhu
Major depression is a serious global health concern; however, the pathophysiology underlying this condition remains unclear. While numerous studies have focused on brain-specific mechanisms, few have evaluated the role of peripheral organs in depression. Here, we show that the liver activates an intrinsic metabolic pathway that can modulate depressive-like behavior. We find that chronic stress specifically increases the protein levels of monomeric and oligo-meric soluble epoxide hydrolase (sEH), a key enzyme in epoxyeicosatrienoic acid (EET) signaling, in the liver. Hepatic deletion of Ephx2 (which encodes sEH) results in antidepressant-like effects, while the hepatic overexpression of sEH induces depressive phenotypes. The activity of sEH in hepatocytes modulates the plasma levels of 14,15-EET, which then interacts with astrocytes in the medial prefrontal cortex to mediate the effects of hepatic Ephx2 deletion. These results suggest that targeting mechanisms underlying the hepatic response to stress would increase our therapeutic options for the treatment of depression.
Fig.1 Effects of AAV-Ephx2 injections.
To investigate the role of the liver in depression, using adeno-associated virus (AAV) and lentivirus (LV) (From
BrainVTA) to achieve different level expression of hepatocyte gene in the CMS mouse model, the results showed that the liver plays an essential role in the pathophysiology of depression, indicating that the liver may play a critical role in regulation of moods.
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