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Regional distribution of cyclooxygenase‐2 in the hippocampal formation in Alzheimer's disease
Author(s) -
Ho Lap,
Pieroni Cristiana,
Winger David,
Purohit Dushyant P.,
Aisen Paul S.,
Pasinetti Giulio Maria
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990801)57:3<295::aid-jnr1>3.0.co;2-0
Subject(s) - hippocampal formation , dentate gyrus , immunostaining , alzheimer's disease , cyclooxygenase , neuroscience , long term potentiation , biology , neurodegeneration , chemistry , endocrinology , medicine , pathology , enzyme , disease , immunohistochemistry , receptor , biochemistry
Cyclooxygenase‐2 (COX‐2), a key enzyme in prostanoid biosynthesis, may represent an important therapeutic target in Alzheimer's disease (AD). In the present study, we explored the regulation of COX‐2 in the hippocampal formation in sporadic AD. Using semiquantitative immunocytochemical techniques, we found that in AD cases (vs. age‐matched controls) neurons of the CA1–CA4 subdivisions of the hippocampal pyramidal layer showed elevation of COX‐2 signal; COX‐2 levels correlated with amyloid plaque density. In contrast, the level of COX‐2 immunostaining in the dentate gyrus granule neurons was not elevated in AD. No expression of COX‐2 in cells with glial morphology was found in any case examined. In parallel, in vitro studies found that neurons derived from transgenic mice with neuronal overexpression of COX‐2 are more susceptible to β‐amyloid (Aβ) toxicity, with potentiation of redox impairment. The results indicate elevated expression of neuronal COX‐2 in subregions of the hippocampal formation in AD and that such elevation may potentiate Aβ‐mediated oxidative stress. J. Neurosci. Res. 57:295–303, 1999. © 1999 Wiley‐Liss, Inc.