β-Amyloid-Mediated Inhibition of NMDA Receptor-Dependent Long-Term Potentiation Induction Involves Activation of Microglia and Stimulation of Inducible Nitric Oxide Synthase and Superoxide

• DOI: 10.1523/jneurosci.0233-04.2004
• Publication Date: 2004-07-07T19:37:03Z
• Authors: Qinwen Wang; Michael J. Rowan; Roger Anwyl
• Keywords: LTP induction; Long-term depression

The mechanisms underlying the inhibition of long-term potentiation (LTP) induction by amyloidβ-peptide (Aβ) were investigated in medial perforant path rat and mouse dentate gyrus vitro . Evidence is presented this study that Aβ-mediated LTP involves activation microglia production reactive oxygen nitrogen species. In control slices, Aβ strongly inhibited NMDA receptor-dependent (NMDAR-dependent) LTP, although not NMDAR-independent or depression (LTD). NMDAR-dependent was prevented minocycline, an agent prevents microglia. involvement inducible nitric oxide synthase (iNOS) shown inability to inhibit iNOS knock-out mice also ability two inhibitors, aminoguanidine 1400W, prevent induction. superoxide scavenger dismutase applied together with catalase. for action on inhibitor NADPH oxidase thus provides evidence inflammatory-type reaction which results thence possibly peroxynitrite, a highly oxidant.