Mechanism of impairment of long-term potentiation by amyloid β is independent of NMDA receptors or voltage-dependent calcium channels in hippocampal CA1 pyramidal neurons

[摘要] beta-Amyloid peptide (A beta) is known to be involved in Alzheimer's disease (AD). Although the fibril form of A beta is known to have neurotoxicity, it has been shown that not only the fibril form but also the oligomer form of A beta may be related to the neuropathophysiology of AD, specifically to memory loss. Some studies have demonstrated that low concentrations of the A beta oligomer impair long-term potentiation (LTP), a cellular model for learning and memory, after short exposure times in vivo and in vitro, although little is known about the mechanism involved in A beta-mediated inhibition of LTP. In this study, we used the patch clamp whole-cell technique in rat hippocampal CA1 pyramidal neurons to study more precisely how the A beta oligomer affects synaptic plasticity. The brief perfusion of slices with a low concentration (1 mu M) of A beta(1-42) significantly impaired UP induction of the excitatory input. The same concentration of A beta did not affect basal transmission or paired-pulse facilitation. We also demonstrated that neither NMDAR-EPSCs nor the voltage-depended calcium channel (VDCC) currents were affected by the same concentration of A beta(1-42) as used in the LTP experiments. These data suggest that A beta mediated impairment of UP induction is independent of NMDARs or VDCCs. (C) 2005 Elsevier Ireland Ltd. All rights reserved.

[发布日期] 2005-12-31

[关键词] Alzheimer's disease;amyloid beta;long-term potentiation (LTP);NMDA receptor;calcium channel