title: Intraneuronally injected amyloid β inhibits long-term potentiation in rat hippocampal slices.
abstract: Extracellular accumulation of amyloid beta (Aβ) is a hallmark of Alzheimer's disease (AD). It has been reported that extracellular perfusion of Aβ inhibits long-term potentiation (LTP), which is strongly related to memory in animal models. However, it has recently been proposed that intracellular Aβ may be the first pathological change to occur in AD. Here, we have investigated the effect on LTP of intracellular injection of Aβ (Aβ(1-40), Aβ(1-42)) into hippocampal pyramidal cells using patch-clamp technique. We found that injection of 1 nM Aβ(1-42) completely blocked LTP, and extracellular perfusion of a p38 MAPK inhibitor or a metabotropic glutamate receptor blocker reversed these blocking effects on LTP. Furthermore, we have examined the effects of different concentrations of Aβ(1-40) and Aβ(1-42) on LTP and showed that Aβ(1-40) required a 1,000-fold higher concentration to attenuate LTP than 1 nM Aβ(1-42). These results indicate that LTP is impaired by Aβ injected into genetically wild-type neurons in the sliced hippocampus, suggesting an acute action of intracellular Aβ on the intracellular LTP-inducing machinery.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nomura
authors.forename: Hajime
authors.initials: H
authors.lastname: Takechi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kato
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides