The Effect And Mechanisms Of Theacrine On Hippocampal Proliferation After Chronic Water Immersion Restraint Stress

Aims: A negative correlation relationship between daily intake of caffeine-containingdrinks and the risk of depression has been found in a relatively large populationsample. Theacrine, a natural purine alkaloid obtained from Camellia assamica var.kucha, is similar to caffeine in chemical. This study aimed to investigate the effect oftheacrine on depression disorder evoked by chronic water immersion restraint stress(CWIRS). Methods: Kunming mice were exposed to CWIRS for three weeks and thedrugs were administrated a week in advance and four weeks. Behavioral tests werecarried out by different behavioral testing instruments and the contents of5-hydroxytryptamine (5-HT) and the corticosterone (CORT) levels were measured byHPLC. Immunostaining method was used to detect the proliferation of neurons in thehippocampus. The further mechanisms were studied using ELISA and westernblotting methods. Results: Results showed that chronic treatment with theacrine,caffeine and fluoxetine significantly counteracted CWIRS-induced depression. Theresult of spontaneous motor-activity test suggested that caffeine had central excitation,but theacrine hadn’t. Meanwhile, theacrine reversed stress-induced elevation ofcorticosterone level and reduction of neural cell proliferation in hippocampus. Furtherstudies indicated that theacrine could activate cAMP/CREB/BDNF/TrkB pathway.Conclusions: Theacrine possessed anti-depression effect without central excitation,which are through preventing the inhibition of neurogenesis caused by stress viaactivating cAMP/CREB/BDNF/TrkB pathway.