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

Abstract

The effect of the β-amyloid peptide (β-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 μM β-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 μM β-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 μM) had no significant effect on baseline synaptic transmission or LTP ( n=4). However, in the presence of SB203580, β-AP (25–35; 1 μM) did not give rise to a reduction in LTP (150±11.8%, n=4). These results suggest that high levels of β-AP (25–35) may inhibit LTP through a pathway involving the p38 MAP kinase.