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 language | English (US) |
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Pages (from-to) | 951-962 |
Number of pages | 12 |
Journal | Experimental Gerontology |
Volume | 42 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2007 |
Externally published | Yes |
Keywords
- Alzheimer
- Aβ
- Inflammation
- JNK
- NO
- p38
ASJC Scopus subject areas
- Biochemistry
- Aging
- Molecular Biology
- Genetics
- Endocrinology
- Cell Biology