Activation of nicotinic alpha(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1DeltaE9 mice.

摘要

Amyloid beta (Abeta) plays a central role in Alzheimer's disease (AD) and binds to the nicotinic alpha(7) receptor (alpha(7) nAChR). Little is known about the degree to which the binding of Abeta to the alpha(7) nAChR influences the role of this receptor in long-term potentiation (LTP), however. We have studied the effect of the partial alpha(7) nAChR agonist SSR180711 on hippocampal slice preparations from normal wild type (Wt) and APP(swe)/PS1DeltaE9 transgenic (Tg) mice. In the hippocampal slices from the 6 months old Wt mice, the application of both nicotine (5muM) and SSR180711 (300nM) resulted in a significant enhancement of LTP expressed in area CA1. However, in the Tg mice the application of SSR180711 did not result in an increase in LTP beyond control levels. The amount of binding of the alpha(7) nAChR ligand 125-I-alpha-bungarotoxin was not different between in Tg and Wt mice. These findings indicate that the alpha(7) nAChR is functionally blocked in the hippocampal neurons, downstream of the alpha(7) nAChR, and that this is likely due to an interaction between the receptor and Abeta, which leads to changes in LTP.