Figure 1

Experimental timelines of short-term (Experiment 1) and sub-chronic (Experiment 2) agmatine treatment. In Experiment 1, wild-type mice were gavaged with 100 μl saline once daily for two days. During the following 7 days, animals were given saline gavage on days 1–5 but intraperitoneal (IP) injection of saline or agmatine at 40 mg/kg once daily on days 6 and 7, whereas others received daily oral gavage of saline or agmatine at 300, 600 and 900 mg/kg. On day 6, all animals were tested in the elevated plus maze (EPM) and open field (OF) 30 minutes post-treatment. On day 7, animals were sacrificed 30 minutes post-treatment followed by blood (plasma) and brain tissue (hippocampus) collection for quantification of L-arginine and its metabolites. In Experiment 2, wild-type and APP/PS1 transgenic mice received oral gavage of saline or agmatine sulfate at 300 mg/kg once daily for 5 days per week for 8 weeks, then once daily for 7 days a week for a further 7 weeks. On day 71, animals were tested in the EPM and OF 24 h after treatment. On day 105, animals were sacrificed 24 hours after the final treatment of day 104 followed by blood and brain tissue collection for agmatine and putrescine quantification.