A PDK-1 allosteric agonist neutralizes insulin signaling derangements and beta-amyloid toxicity in neuronal cells and in vitro
Fig 3
PS48 partly restores the suppression of LTP by Aβ42.
A. Day 14 rat prefrontal cortex (PFC) exposed to Aβ oligomers (0.5 μM) or Aβ plus PS48 (10 μM). Superimposed representative single recordings made under conditions 1 through 5, as noted. Control is DMSO-vehicle. EPSPs recorded from layer 2; stimuli (32 μA = ½ max ampl., 2 Hz) applied to layer 5. Aβ completely suppressed LTP (5 vs. 1). PS48 in the prsence of Aβ restored 68 ± 18% of control potentiated EPSP (1 hour perfusion, condition 2). A 3 hour application however showed near complete run-down (3). Aβ and Aβ/PS48 experiments were restored to control LTP levels after washout (4). B. Quantification of LTP data. Bar graph (left). LTP induction shown as mean % change (increase or decrease) from baseline (± SEM). n independent replicates are noted. Scatter graph (right) gives means of individual experiments and group averages as unadjusted % baseline values (normalized at 100%). All concentrations Aβ> 1 nM (high dose, 2.5–500 nM) completely abrogated LTP. PS47 is an inactive isomer control (n = 2). n replicates as shown. *** p < .0001 Aβ alone (high dose) vs control, ** p < .01 PS48 treatment vs Aβ alone (high doses), * p < .05 PS48 treatment vs. P47 control (Aβ high doses); ANOVA and Tukey’s tests (see text for additional statistical details).