Regional distribution of cyclooxygenase‐2 in the hippocampal formation in Alzheimer's disease

Abstract

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 beta-amyloid (Abeta) 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 Abeta-mediated oxidative stress.

Fear recognition deficits after focal brain damage

“…Recent studies have documented a correlation between cognitive function and certain medial temporal-lobe structures, but some of the studies have involved small numbers of subjects. 3,32,33 The combined normal control and AD data demonstrated good relationships between relevant medial temporal-lobe structures, in particular the hippocampus, and a variety of acquisition and recall functions. The volume of the hippocampus was the best predictor of delayed recall and learning on both list-learning procedures and paragraph-and geometric shape-recall tasks, as would be expected from known structural-functional relationships.…”

“…Recent studies suggest that cyclooxygenase (COX)-2 may be involved in neurodegenerative mechanisms in the AD brain, 31,32 and may represent a specific therapeutic target for anti-inflammatory drugs. Glucocorticoids inhibit the induction of brain COX-2 33 ; however, the necessary dose is unknown.…”

Acute hepatocellular and cholestatic injury in a patient taking celecoxib

“…They were also found to have a role in the pathogenesis of Alzheimer's disease 9. In future, COX-2 inhibitors may have a role in the chemoprophylaxis of many cancers 10.…”

Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function

“…The two Cox forms are known to be differentially regulated; Cox1 is often expressed constitutively while Cox2 expression is induced by proinflammatory conditions. In the brain, however, Cox2 is constitutively expressed by neurons (212, 512), participates in modulating synaptic plasticity (53, 464), and conditionally can either inhibit or promote cell death (74, 85, 237, 322, 451). A link between α4 nAChRs and Cox2 was suggested by the observation that interneurons in the hippocampus coexpress both proteins (165).…”