beta-Amyloid produces a delayed NMDA receptor-dependent reduction in synaptic transmission in rat hippocampus.
The delayed effect of in vivo injection of beta-amyloid on glutamatergic synaptic transmission was investigated in the rat hippocampus. The amplitude of field excitatory postsynaptic potentials recorded in the CA1 region of awake rats was reduced 24 h after the injection of beta-amyloid (1-40) (0.4 or 3.5 nmol i.c.v.). The effect lasted for at least 5 days and was prevented by treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist CPP (7 mg kg-1 x 2, i.p.). Similar results were obtained ex vivo in the dentate gyrus. There was no change in the ability to induce long-term potentiation. These results provide direct evidence that beta-amyloid produced a delayed reduction in the function of glutamatergic synapses, probably as a result of an initial over-activation of the NMDA receptor-mediated component of transmission.
Cullen
W K
WK
Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland.
Wu
J
J
Anwyl
R
R
Rowan
M J
MJ
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid