FIGURE 2.
GW0742 ameliorates memory deficits in APP/PS1-mice concomitant with increased Cpt1a expression levels in the brain. (a) Schematic representation of hippocampus-dependent contextual memory test. The mice were daily administered p.o. with vehicle (veh) or 30 mg/kg GW0742 (GW42) for 14 days. The mice were trained in a conditioning chamber for 12 min receiving four foot shocks (1.0 mA, 2 s) in 1-min interval for contextual hippocampal memory formation. After 24 hr, the mice were placed into the same chamber and memory formation was evaluated by scoring freezing behavior for 5 min. (b) Percentage of freezing time to vehicle treated wild type (wt) mice. n = 32 wt veh, n = 7 wt GW42, n = 8–10 APP/PS1 (tg) veh and GW42. (c) Behavioral activity was measured as mean velocity in OF test 1 day before and 14 days after the start of GW0742 administration. Mean velocity is shown as a fold change to wt vehicle at each time point. n = 4–5. (d) Change in the body weight of mice before and after the treatment. n = 7–9. (e) Relative gene expression levels of Cpt1a in cortex, shown as fold change to wt vehicle. (f ) Respective gene expression levels of Cpt2. n = 8. All data are presented as mean ± SEM with *p < .05 and **p < .01 as analyzed by t test or two-way anova followed by Bonferroni post hoc test. cpt1a = carnitine palmitoyltransferase 1a