Curcuminoids Rescue Long-Term Potentiation Impaired by Amyloid Peptide in Rat Hippocampal Slices

Curcuminoids are vital constituent of turmeric, with therapeutic potential in the treatment of Alzheimer's disease. Electrically, stimulus train-elicited plastic changes in hippocampal CA1 excitability were used as an experimental paradigm to study the effects of curcuminoid mixture and individual components on functional failure induced by Ab peptide in vitro. Electrical stimulation was applied on Schaffer collaterals, and population spikes (PS) were recorded from stratum pyramidale. To induce long-term potentiation (LTP) of PS, primed burst stimulation (PBs) was used. A beta peptide inhibited PS LTP induction. Sinking PS LTP due to A beta peptide was rescued when curcuminoid mixture was applied before PBs only at lower dose (0.1 mu M) resulting in PS potentiation to 127.42% +/- 1.83% at 5 min and 123.98% +/- 1.06% at 60-min post-PBs. Similarly, when bisdemethoxycurcumin was applied, PS LTP was induced and lasted only at a single dose (0.1 mu M). Demethoxycurcumin was effective at a middle dose (1 mu M), so that the PS amplitude was changed to 140.15% +/- 2.68% and 129.82% +/- 0.44% at 5 and 60 min, respectively. PS LTP was effectively induced in the presence of curcumin at middle and high doses (1 and 30 mu M) with resultant PS LTP to 155.68% +/- 1.23% and 127.72% +/- 1.23%, respectively, at 60-min post-PBs. These results showed that curcuminoids can restore susceptibility for plastic changes in CA1 excitability that is injured by exposure to A beta peptide and rescue sinking PS LTP in A beta-peptide-exposed hippocampal CA1 neurons. Synapse 65: 572-582, 2011. (C) 2010 Wiley-Liss, Inc.