title: Requirement of α7 nicotinic acetylcholine receptors for amyloid β protein-induced depression of hippocampal long-term potentiation in CA1 region of rats in vivo.
abstract: The high density of senile plaques with amyloid beta protein (Aβ) and the loss of cholinergic neurons in the brain are the dominated pathological characteristics of Alzheimer's disease (AD). However, the active center of Aβ, especially the cholinergic mechanism underlying the Aβ neurotoxicity, is mostly unknown. This study examined the effects of different Aβ fragments on hippocampal long-term potentiation (LTP) and investigated its probable α7 nicotinic acetylcholine receptors (nAChRs) mechanism. The results show that: (1) intracerebroventicular injection of Aβ25-35 or Aβ31-35 significantly and similarly suppressed hippocampal LTP in CA1 region in rats; (2) choline, a selective α7 nAChR agonist, did not affect the LTP induction but enhanced LTP suppression induced by Aβ31-35; and (3) methyllycaconitine, a specific α7 nAChR antagonist, slightly suppressed hippocamal LTP but effectively prevented against Aβ31-35-induced LTP depression in the presence of Aβ31-35. These results indicate that: (1) the amino acid sequence 31-35 of the Aβ peptide might be a shorter active sequence in the full length molecule; (2) α7 nAChRs are required for the Aβ-induced suppression of hippocampal LTP. Thus, this study not only provides a new insight into the mechanism by which Aβ impairs synaptic plasticity but also strongly suggests that sequence 31-35 in Aβ molecule and α7 nAChRs in the brain might be potential therapeutic targets for the treatment of AD.
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Li
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Wu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D016229:Amyloid beta-Peptides; C579165:Chrna7 protein, rat; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C074636:amyloid beta-protein (25-35); C113042:amyloid beta-protein (31-35)