Divergent effects of Aβ1-42 on ionotropic glutamate receptor-mediated responses in CA1 neurons in vivo

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Abstract

Aggregated Aβ1-42 is hypothesized to be the central cause of Alzheimer's disease. However, early changes in synaptic activity may be detected in the disease long before a significant cell loss is manifested. Despite the fact that Aβ1-42 interference with long-term potentiation (LTP) and the field excitatory postsynaptic potential (fEPSP) is well documented, the exact mechanism of these events remains to be clarified. Here we studied the effects of iontophoretically applied Aβ1-42 on the neuronal firing evoked in vivo on the CA1 hippocampal neurons of Wistar rats by different agonists of the ionotropic glutamate receptors: N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid (KA). NMDA elicited firing enhanced in all of the measured cells; in contrast, the AMPA-mediated responses decreased significantly after Aβ1-42 ejection. The changes in KA-evoked responses to Aβ1-42 revealed two types of cells. In the first type, the KA-mediated firing remained at the control level, while in the second type, Aβ1-42 attenuated the KA-evoked responses. A protective pentapeptide, Leu-Pro-Tyr-Phe-Asp-amide, was used to verify the specificity of these β-amyloid-elicited effects. The pentapeptide protected against the modulatory effects of Aβ1-42 on the NMDA and AMPA responses. In conclusion, we have shown that Aβ1-42 exerts divergent effects on the activity of the ionotropic glutamate receptors in vivo. These results suggest that the LTP disruption and fEPSP attenuation seen after Aβ1-42 application are in part due to the altered function of these receptors.

Original languageEnglish
Pages (from-to)120-126
Number of pages7
JournalBrain research
Volume1062
Issue number1-2
DOIs
Publication statusPublished - Nov 16 2005

Keywords

  • Alzheimer's disease
  • Hippocampus
  • Microiontophoresis
  • Single-unit recording

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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