Beta-amyloid-mediated inhibition of NMDA receptor-dependent long-term potentiation induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide
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2004Access:
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Wang Q, Rowan MJ, Anwyl R, Beta-amyloid-mediated inhibition of NMDA receptor-dependent long-term potentiation induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide, The Journal of Neuroscience, 24, 27, 2004, 6049, 6056Download Item:
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Abstract:
The mechanisms underlying the inhibition of long-term potentiation (LTP) induction by amyloid
-peptide (A
) were investigated in the
medial perforant path of the rat and mouse dentate gyrus
in vitro
. Evidence is presented in this study that the A
-mediated inhibition of
LTP induction involves activation of microglia and production of reactive oxygen and nitrogen species. In control slices, A
strongly
inhibited induction of NMDA receptor-dependent (NMDAR-dependent) LTP, although not induction of NMDAR-independent LTP or
long-term depression (LTD). The inhibition of NMDAR-dependent LTP was prevented by minocycline, an agent that prevents activation
of microglia. The involvement of inducible nitric oxide synthase (iNOS) was shown by the inability of A
to inhibit LTP induction in iNOS
knock-out mice and also by the ability of two iNOS inhibitors, aminoguanidine and 1400W, to prevent the A
-mediated inhibition of LTP
induction. The A
-mediated inhibition of LTP induction also was prevented by the superoxide scavenger superoxide dismutase applied
together with catalase. Evidence for involvement of superoxide in the action of A
on LTP induction was shown by the ability of an
inhibitor of NADPH oxidase to prevent the A
-mediated inhibition of LTP induction. The study thus provides evidence that the A
-
mediated inhibition of LTP induction involves an inflammatory-type reaction in which activation of microglia results in the production
of nitric oxide and superoxide and thence possibly peroxynitrite, a highly reactive oxidant
Author's Homepage:
http://people.tcd.ie/ranwylhttp://people.tcd.ie/mrowan
Description:
PUBLISHED
Author: ANWYL, ROGER; ROWAN, MICHAEL
Type of material:
Journal ArticleCollections:
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The Journal of Neuroscience24
27
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Full text availableKeywords:
amyloid -protein; LTP; dentate gyrus; microglia; inducible nitric oxide; superoxide; caspasesSubject (TCD):
Ageing , NeuroscienceDOI:
http://dx.doi.org/10.1523/JNEUROSCI.0233-04.2004Licences: