Neuroprotective effects of shrimp peptides by improving synaptic plasticity through Adcy5/PKA/p-CREB based on proteomic techniques

There is currently a great deal of interest in developing neuroprotective peptides to address memory impairment and cognitive decline. Although the shrimp peptide Gln-Met-Asp-Asp-Gln (QMDDQ) has been demonstrated to have neuroprotective activity by cellular assays, the molecular regulatory mechanism in animals remains unclear. In this study, we explored the neuroprotective effects of QMDDQ in mice with scopolamine-induced memory impartment using behavioral tests, tissue staining techniques, proteomics, immunofluorescence, and Western blotting. The results of the study showed that QMDDQ was able to shorten the escape latency, reduce the number of electric shocks, and improve the behavioral performance of mice. The neuronal damage in CA1, CA3 and Dentate Gyrus regions was better repaired, and QMDDQ also increased the content of acetylcholine in the hippocampus with the increase of the gavage dose, and the activity of acetylcholinesterase was inhibited. Proteomics data showed that a total of 62 differential proteins were identified in the model and QMDDQ groups, with KEGG pathway enrichment showed significant changes in 40 pathways such as the cAMP signaling pathway, as verified by the key protein adenylate cyclase 5 (Adcy5). The results suggested that QMDDQ improved synaptic plasticity through the Adcy5/PKA/p-CREB pathway, thus exerting a neuroprotective effect protective effect.