| Dr. Harman 2005-09-24, 12:37 pm |
| wata R, Kitagawa K, Zhang NY, Wu B, Inagaki C.
Department of Pharmacology, Kansai Medical University, Fumizono-cho
10-15, Moriguchi, Osaka 570-8506, Japan.
Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) such as
ibuprofen reportedly decrease a risk for the progression of Alzheimer's
disease (AD), whose mechanisms are still controversial. We previously
reported that pathophysiological concentrations (1-10 nM) of amyloid
beta proteins (Abetas) increased intracellular Cl- concentration
([Cl-]i) and aggravated glutamate neurotoxicity in the rat brain
neuronal culture. In this study, we examined the effects of therapeutic
concentrations of ibuprofen and other drugs with cyclo-oxygenase
(COX)-1 and/or COX-2 inhibiting activities on 10 nM Abeta25-35-induced
changes in cultured rat hippocampal neurons. Ibuprofen (10-100 microM)
dose-dependently inhibited the Abeta25-35-induced increase in [Cl-]i in
pyramidal cell-like neurons. Not only ibuprofen, aspirin (100 microM),
indomethacin (50 microM), and selective COX-1 or COX-2 inhibitor (10 nM
ketrolac or 2 microM NS398) also blocked the Abeta-induced increase in
neuronal [Cl-]i, though such effects of COX-2 preferring drugs were
limited in aggregated Abeta-induced changes. Further, ibuprofen as well
as selective COX-1 or COX-
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