Chronic Royal Jelly Administration Induced Antidepressant-Like Effects Through Increased Sirtuin1 and Oxidative Phosphorylation Protein Expression in the Amygdala of Mice

Background: Major depressive disorder (MDD) is a common psychological disorder worldwide. However, one-third of patients with MDD are resistant to the present anti-depressant medicine, which regulates monoamine contents in the brain. Thus, another drug target is strongly required. Much evidence strongly suggests that sirtuin1, which is the key factor in regulating the mitochondrial activity, may be implicated in MDD. Objective: Since it is suggested that royal jelly (RJ) ameliorated depressive-like behavior and affected mitochondrial activity in mice, we hypothesized that RJ could be an alternative medicine against MDD, which acts via sirtuin1 signaling to improve mitochondrial activity. Methods: In the present study, we applied a mouse model of MDD to investigate the effect of RJ on the depressive-like behavior and the sirtuin1 signaling on mitochondrial activity. Results: Our results indicated that either the oral administration of RJ for 12 days or single intracerebroventricular (i.c.v.) injection decreased the duration of immobility in the tail suspension test, which suggested that RJ had an antidepressant-like effect. Moreover, sirtuin1 protein expression increased in mice following RJ treatment in the amygdala region, but not in the other brain regions. Similarly, the expressions of oxidative phosphorylation (OXPHOS) related proteins increased in the amygdala regions, but not in the hippocampal regions. Conclusion: The increase of sirtuin1 and OXPHOS protein expression may at least in part contribute to the antidepressant-like effect of the RJ pathway, and RJ may have the potential to be a novel anti-depressant drug.