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

Izumi Nomura, Hajime Takechi, Nobuo Kato

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)2526-2531
Number of pages6
JournalJournal of Neurophysiology
Volume107
Issue number9
DOIs
Publication statusPublished - 01-05-2012
Externally publishedYes

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Long-Term Potentiation
Amyloid
Alzheimer Disease
Perfusion
Injections
Metabotropic Glutamate Receptors
Pyramidal Cells
Patch-Clamp Techniques
p38 Mitogen-Activated Protein Kinases
Hippocampus
Animal Models
Neurons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

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Intraneuronally injected amyloid beta inhibits long-term potentiation in rat hippocampal slices. / Nomura, Izumi; Takechi, Hajime; Kato, Nobuo.

In: Journal of Neurophysiology, Vol. 107, No. 9, 01.05.2012, p. 2526-2531.

Research output: Contribution to journalArticle

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