SB203580, the p38 mitogen-activated protein kinase inhibitor blocks the inhibitory effect of beta-amyloid on long-term potentiation in the rat hippocampus

Abstract

The effect of the beta-amyloid peptide (beta-AP) 25-35 and SB203580, the p38 mitogen-activated protein (MAP) kinase inhibitor, were investigated on long term potentiation (LTP) in the dentate gyrus of the rat hippocampal slice. In the presence of 1 microM beta-AP (25-35) basal synaptic transmission was reduced to 88.9+/-5.2% of control (n=4, P<0.5). Tetanic stimulation of control slices gave rise to a robust LTP (139+/-4%, n=5, P<0.05). 1 microM beta-AP (25-35) was found to inhibit this LTP (104.0+/-4.5% at 90 min; n=4, P<0.05). Perfusion of SB203580 alone (1 microM) had no significant effect on baseline synaptic transmission or LTP (n=4). However, in the presence of SB203580, beta-AP (25-35; 1 microM) did not give rise to a reduction in LTP (150+/-11.8%, n=4). These results suggest that high levels of beta-AP (25-35) may inhibit LTP through a pathway involving the p38 MAP kinase.