Suppressive action produced by beta-amyloid peptide fragment 31-35 on long-term potentiation in rat hippocampus is N-methyl-D-aspartate receptor-independent: it's offset by (-)huperzine A.
Extracellular recordings of field potential from CA1 region of rat hippocampal slices were used to observe the effects of a shorter synthetic fragment of beta-amyloid peptide (A beta31-35) on the induction of long-term potentiation (LTP) and the action of (-)huperzine A, a potent acetylcholinesterase (AChE) inhibitor on these processes was also observed. The results showed that: (1) 0.1 microM A beta31-35 suppressed the induction of LTP in a similar mode as the longer fragment A beta25-35, did, while they did not change the amplitude of the baseline population spike (PS); (2) when PSs were recorded separately in Mg2+-free medium, which unveils the N-methyl-D-aspartate (NMDA)-mediated responses, both A beta31-35 and A beta25-35 showed little effect on the components of multiple PSs; (3) two concentrations of 0.1 microM or 1.0 microM (-)huperzine A showed no effects on the PS amplitude while the latter could enhance the LTP and (4) co-administration of (-)huperzine A with 0.1 microM concentration could block most of the suppressive action induced by A beta31-35 or A beta25-35 upon the LTP. The results suggest that the shorter fragment A beta31-35, is long enough to suppress the induction of LTP and these two fragments might suppress the induction of LTP through a NMDA receptor-independent pathway that involves cholinergic terminals in hippocampus.
Ye
L
L
Department of Neurobiology, Shanxi Medical University, Taiyuan, People's Republic of China.
Qiao
J T
JT
D000470:Alkaloids; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012717:Sesquiterpenes / Q000494:pharmacology*
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D012717:Sesquiterpenes; C113042:amyloid beta-protein (31-35); C113041:amyloid beta-protein (35-25); C050426:huperzine A