Diterpene Ginkgolides Exert an Antidepressive Effect Through the NT3-TrkA and Ras-MAPK Pathways

Abstract

Depression is a highly prevalent mental illness that severely impacts the quality of life of affected individuals. Our recent studies demonstrated that Diterpene Ginkgolides (DG) have antidepressive effects in mice. However, the underlying molecular mechanisms remained much unclear. In this study, we assessed the antidepressive effects of chronic DG therapy in rats by evaluating depression-related behaviors, and we examined potential side effects using biochemical indicators. Furthermore, we performed an in-depth molecular network analysis of gene-protein-metabolite interactions on the basis of metabolomics. Chronic DG treatment significantly ameliorated the depressive-like behavioral phenotype. Furthermore, the neurotrophin signaling-related NT3-TrkA and Ras-MAPK pathways may play an important role in the antidepressive effect of DG in the hippocampus. These findings provide novel insight into the mechanisms underlying the antidepressive action of DG, and should help advance the development of new therapeutic strategies for depression. Funding: This work was supported by the National Key R&D Program of China (Grant No. 2017YFA0505700), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No.2019PT320002), the National Natural Science Foundation of China (Grant No. 8190050191), the National Key Program International Cooperation Project (No. 81820108015) and the Natural Science Foundation of Chongqing, China (Grant No. cstc2019jcyj-msxm0236). Declaration of Interest: The authors declare that they have no conflicts of interest. Ethical Approval: All animal experiments were approved by the Ethics Committee of Chongqing Medical University (permit number: 20120126), and were in accordance with the Guide for the Care and Use of Laboratory Animals.