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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / physiology*
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Animals
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Enzyme Inhibitors / pharmacology*
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Excitatory Postsynaptic Potentials / drug effects*
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Excitatory Postsynaptic Potentials / physiology
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Hippocampus / drug effects
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Hippocampus / enzymology
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Hippocampus / physiology*
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Imidazoles / pharmacology*
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In Vitro Techniques
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Long-Term Potentiation / drug effects*
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Long-Term Potentiation / physiology
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Male
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Mitogen-Activated Protein Kinases / metabolism
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Peptide Fragments / antagonists & inhibitors*
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Peptide Fragments / physiology*
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Pyridines / pharmacology*
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Rats
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Rats, Wistar
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Synaptic Transmission / drug effects
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p38 Mitogen-Activated Protein Kinases
Substances
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Amyloid beta-Peptides
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Enzyme Inhibitors
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Imidazoles
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Peptide Fragments
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Pyridines
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amyloid beta-protein (25-35)
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580