SB203580, the p38 mitogen-activated protein kinase inhibitor blocks the inhibitory effect of beta-amyloid on long-term potentiation in the rat hippocampus.
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.
Saleshando
G
G
Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College, Earlsfort Terrace, Dublin 2, Ireland.
O'Connor
J J
JJ
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; C074636:amyloid beta-protein (25-35); D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580