β-Amyloid(1-42) induces a reduction in the parallel fiber responses of Purkinje cells: Possible involvement of pro-inflammatory processes

Nicolas Arbez, Vanessa Gautheron, Bernard Brugg, Jean Mariani, Catherine Rovira

Research output: Contribution to journalArticle

Abstract

In Alzheimer's disease there is an increased production of the toxic β-amyloid peptides (Aβ), especially the longer forms such as Aβ(1-42). Using the patch-clamp technique we have studied the contribution of early pro-inflammatory processes to the acute effects of 1 μM Aβ(1-42) on the parallel fiber EPSC (PF-EPSC) of Purkinje cells in cerebellar slices. Aβ(1-42) induces a decrease in the PF-EPSC amplitude. This decrease is accompanied by a decrease in the frequency and amplitude of the miniature EPSCs, suggesting that Aβ acts at both pre- and post-synaptic sites. In the presence of L-NAME, a nitric oxide synthase inhibitor, the effects of Aβ were partially blocked. The frequency of mEPSCs was unchanged while Aβ still reduced the mEPSCs amplitude. The anti-inflammatory agent flurbiprofen blocked the depressant action of Aβ on the mEPSCs amplitude but not its effect on mEPSCs frequency. Both a p38 inhibitor (SB203580) and a JNK inhibitor (SP600125) reverse the effects of Aβ as an increase in the mEPSCs frequency and amplitude was observed. This study provides evidence that the Aβ-induced depression of the PF-EPSCs was mediated via an activation of JNK and p38 and by the action of NO and raises the possibility of the involvement of an early pro-inflammatory process.

Original languageEnglish (US)
Pages (from-to)951-962
Number of pages12
JournalExperimental Gerontology
Volume42
Issue number10
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Keywords

  • Alzheimer
  • Inflammation
  • JNK
  • NO
  • p38

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Fingerprint Dive into the research topics of 'β-Amyloid(1-42) induces a reduction in the parallel fiber responses of Purkinje cells: Possible involvement of pro-inflammatory processes'. Together they form a unique fingerprint.

  • Cite this