Fig. 3.

CP2 treatment improves synaptic function and LTP in 3xTg-AD mice. A) Experimental setup for stimulation-evoked local field potential (LFP) measurement in the hippocampal acute slice. The stimulation (Stim.) electrode was placed at the Schaffer collaterals and the recording (Rec.) electrode was placed at the striatum radiatum in the CA1 region. To induce LTP, three tetanic stimulations (100 Hz, 60μs-pulse width for 1 s) were applied with 3-s intervals. In the slice, LTP was induced and maintained over 30–50 min. Slope of EPSPs was measured and results normalized to the average value established during the 30 min baseline period. Recording continued for at least 60 min following a tetanic stimulation and the first 30 min was used to calculate the LTP. B) CP2 treatment improves LTP formation in CP2-treated 3xTg-AD female mice. Traces represent mean±SEM per time. N= 2-3 slices from 3-5 mice per group. C) LTP intensity in CP2-treated female 3xTg-AD mice compared to vehicle-treated counterparts at 30 min after the stimulation. N= 2-3 slices from 3-5 mice per group. D) Representative western blot images of protein markers involved in synaptic function of dendritic spines in the brain tissue of CP2- and vehicle-treated female 3xTg-AD mice. N= 4–7 mice per group. E) Quantification of western blot data from (D) showing a percent of changes in protein expression after CP2 treatment in NTG and 3xTg-AD mice, relative to the levels in vehicle-treated NTG counterparts. Significant increase was observed in levels of synaptophysin (Syn), PSD95, and GluA1 and GluN2B phosphorylation. No changes were detected in total levels of GluA1 and GluN2B. F) Representative western blot images of protein markers involved in synaptic function of dendritic spines in the brain tissue of CP2- and vehicle-treated male 3xTg-AD mice. N= 4–7 mice per group. G) Quantification of western blot data from (F) showing a percent of changes in protein expression after CP2 treatment in NTG and 3xTg-AD mice, relative to the levels in vehicle-treated NTG counterparts. Significant increase was observed in levels of Syn and PSD95, with no improvement in GluN2B phosphorylation. Differences between individual groups were analyzed by one-way ANOVA, with Fisher‘s LSD post-hoc test. Data are presented as mean±SEM. ^*p < 0.05, ^**p < 0.01.