Lycopene Alleviates Depression-Like Behavior in Chronic Social Defeat Stress-Induced Mice by Promoting Synaptic Plasticity via the BDNF–TrkB Pathway

Abstract

Lycopene is a natural plant extract widely studied for its powerful antioxidant and neuroprotective effects. Emerging evidence suggests that it also possesses potential antidepressant properties. Compared to commonly used clinical antidepressants, lycopene offers higher safety; however, its underlying mechanisms remain unclear. Therefore, this study aims to explore the mechanisms through which lycopene exerts its antidepressant effects. We employed the chronic social defeat stress (CSDS) model to induce depressive-like behaviors in mice, followed by lycopene treatment (20 mg/kg). Based on previous research, we focused on synaptic plasticity by examining the expression of synaptic proteins in the hippocampus to uncover potential mechanisms. The results showed that CSDS induced synaptic plasticity impairments in the hippocampus but lycopene treatment significantly improved these synaptic deficits and reversed the depressive-like behaviors induced by CSDS. Moreover, lycopene treatment upregulated the expression of brain-derived neurotrophic factor (BDNF) and reduced the activity of BDNF–TrkB/pTrkB pathway in the hippocampus. These molecular changes were consistent with changes in synaptic-related proteins, suggesting that lycopene may enhance synaptic plasticity via the BDNF–TrkB/pTrkB signaling pathway. This study explored the mechanisms underlying depressive-like behaviors induced by CSDS in mice and provided preclinical evidence that lycopene may serve as a potential antidepressant. It offers an effective avenue for the development of novel antidepressant therapies.