Figure 1. Flow-chart of experimental design. C57BL/6NJ mice were treated with 0, 0.5, 1.5 or 4.5 μg Saxitoxin (STX) equivalents/kg body weight in the drinking water for 3 months. The mice were sacrificed after behavioral tests, and brain hippocampal tissues were isolated for further HE staining and proteomic analysis. Protein was pooled from six animals in each group (Marked as CT, Low, Middle, High) and was digested into peptides. The peptides were further labeled with 6-plex TMT and HPRP fractionation followed by LC-MS/MS analysis. Proteomics analysis was performed by using PEAKS 8.5 software, and bioinformatics analysis. Including heat map, GO, STRING and KEGG pathway was were performed using DAVID 6.8 and OmicShare.