With the increase of social stress and brain aging, memory impairment has become a serious problem. Previous studies have shown preliminary neuroprotective evidence of sea cucumber peptides (SCP) by enhancing behavioral performance and modulating cholinergic system. Here, we further investigated the neuroprotective molecular mechanism of SCP in scopolamine-induced memory impairment mice. Passageway-water-maze and passive-avoidance test revealed that SCP enhanced memory in dose-dependent manner. Therefore, mice hippocampus, derived from high-dose of SCP and Model groups, were analyzed by proteomics. According to the GO functional classification, we further found that SCP increased ACh level, prevent neuronal damage, and improved synapse plasticity. The KEGG pathway enrichment revealed significant up-regulations of dopaminergic/serotonergic synapse and synaptic vesicle cycle, which were validated by key proteins (TH and VMAT2) and downstream mediators (serotonin and dopamine). Overall, this study indicated that SCP protected against memory impairment by improving synapse plasticity and regulating dopamine/serotonin metabolization via TH/VMAT2 pathway.
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