Fig. 6: Systemic administration of PF4 rescues hippocampal learning and memory in aged mice.

a Experimental design of the novel object location (NOL) and fear conditioning (FC) tasks. b Schematic illustration of the NOL arena. c Mice from both treatment groups explored both objects during the first minute of the test session (saline n = 22 mice; PF4 n = 23 mice). d PF4-treated mice (blue) spent more time at the novel location and visited the moved object more frequently (saline n = 22 mice; PF4 n = 23 mice). e Schematic illustration of the FC paradigm. f PF4-treated mice showed a higher freezing response in the FC task (saline n = 22 mice; PF4 n = 23 mice). g PF4-treated mice showed higher freezing behaviour in the fear recall test (saline n = 22 mice; PF4 n = 23 mice). h Experimental design of the active place avoidance (APA) task. i Schematic illustration of the APA arena with angled shock zone (grey) and visual cues. j Representative paths of mice in the APA arena, with red circles indicating the shocks received when entering the shock zone (red lines). k PF4-treated mice (blue) showed a reduction of entrances into the shock zone compared to saline-treated mice (black). Performance of individual mice on day 5 is shown on the right (n = 18 mice per group). Further improvements were observed in the number of shocks (l), entries into the shock zone per distance travelled (m), and time to first (n) and second (o) entrance into the shock zone (n = 18 mice per group). Bars represent mean ± SEM. Statistical analysis was performed using unpaired Student’s two-tailed t tests in (d, g, k–m), and two-tailed Mann–Whitney U tests in (n, o) (right panels, *p < 0.05, **p < 0.01). Two-way repeated measures ANOVAs with Sidak post hoc comparison were performed in (f, k–o) (left panels, effect of treatment *p < 0.05, **p < 0.01, Sidak comparison ^#p < 0.05, ^##p < 0.01). i.v. intravenous. Source data are provided as Source Data file.