Intraneuronally injected amyloid beta inhibits long-term potentiation in rat hippocampal slices

Izumi Nomura, Hajime Takechi, Nobuo Kato

研究成果: ジャーナルへの寄稿学術論文査読

26 被引用数 (Scopus)


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 (Aβ1-40, Aβ1-42) into hippocampal pyramidal cells using patch-clamp technique. We found that injection of 1 nM Aβ1-42 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 Aβ1-40 and Aβ1-42 on LTP and showed that Aβ1-40 required a 1,000-fold higher concentration to attenuate LTP than 1 nM Aβ1-42. 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.

ジャーナルJournal of Neurophysiology
出版ステータス出版済み - 01-05-2012

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 生理学


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