Activation of nicotinic α(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1ΔE9 mice.
Amyloid β (Aβ) plays a central role in Alzheimer's disease (AD) and binds to the nicotinic α(7) receptor (α(7) nAChR). Little is known about the degree to which the binding of Aβ to the α(7) nAChR influences the role of this receptor in long-term potentiation (LTP), however. We have studied the effect of the partial α(7) nAChR agonist SSR180711 on hippocampal slice preparations from normal wild type (Wt) and APP(swe)/PS1ΔE9 transgenic (Tg) mice. In the hippocampal slices from the 6 months old Wt mice, the application of both nicotine (5μM) 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 α(7) nAChR ligand 125-I-α-bungarotoxin was not different between in Tg and Wt mice. These findings indicate that the α(7) nAChR is functionally blocked in the hippocampal neurons, downstream of the α(7) nAChR, and that this is likely due to an interaction between the receptor and Aβ, which leads to changes in LTP.
Department of Anatomy, University of Aarhus, Wilhelm Meyers Allé, 8000 Århus C, Denmark.
Andreas
A
Söderman
Jens D
JD
Mikkelsen
Mark J
MJ
West
Ditte Z
DZ
Christensen
Morten S
MS
Jensen
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016564:Amyloid beta-Protein Precursor; D019086:Bridged Bicyclo Compounds, Heterocyclic; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; C470005:PS1D protein, mouse; D016601:RNA-Binding Proteins; D011978:Receptors, Nicotinic; D012269:Ribosomal Proteins; C516833:SSR180711; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine