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

Abstract

Background

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 antidepressant effects in mice. However, the underlying molecular mechanisms remained much unclear.

Methods

In this study, we assessed the antidepressant effects of chronic DG therapy in rats by evaluating depression-related behaviors, we also 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.

Results

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 antidepressant effect of DG in the hippocampus.

Conclusion

These findings provide novel insight into the mechanisms underlying the antidepressant action of DG, and should help advance the development of new therapeutic strategies for depression.

Keywords:

• diterpene ginkgolides
• antidepressant
• neurotrophin
• hippocampus
• NT3-TrkA and Ras-MAPK pathways

Acknowledgments

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. 81901398), the National Key Program International Cooperation Project (No. 81820108015) and the Natural Science Foundation of Chongqing, China (Grant No. cstc2019jcyj-msxmX0025).

Disclosure

The authors declare that they have no conflicts of interest in this work.