Linked Life Data

16753269

Source:http://linkedlifedata.com/resource/pubmed/id/16753269

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-8-4
pubmed:abstractText
Administration of non-steroidal anti-inflammatory agents reduces the risk of developing Alzheimer's disease in normal aging populations, an effect that may occur from inhibition of the cyclooxygenases, the rate-limiting enzymes in the formation of prostaglandins. In this study, we investigated whether increased activity of cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, potentiates disease progression in a transgenic mouse model of Alzheimer's disease. To study the functional effects of COX-2 activity, male and female bigenic mice (amyloid precursor protein with Swedish mutation [APPswe]-presenilin-1 protein with deletion of exon 9 [PS1dE9] and trigenic COX-2/APPswe-PS1dE9) were behaviorally tested +/-administration of the selective COX-2 inhibitor celecoxib. Behavioral testing included a three-trial Y maze that measures spatial working and recognition memories and an open field task that tested levels of hyperactivity. Overexpression of COX-2 in APPswe-PS1dE9 mice resulted in specific deficits in spatial working memory in female but not male mice. These sex-specific deficits were abolished by pharmacological inhibition of COX-2 activity. Importantly, COX-2-associated deficits were dependent on co-expression of all three transgenes since COX-2 single transgenic and APPswe-PS1dE9 bigenic mice showed normal memory. Quantification of amyloid plaque load and total Abeta 40 and 42 peptides did not reveal significant differences in trigenic versus bigenic mice treated with either vehicle or celecoxib. Taken together, these data indicate an interaction between the effects of COX-2 and Abeta peptides on cognition that occurs in a sex-specific manner in the absence of significant changes in amyloid burden. These findings suggest that pathological activation of COX-2 may potentiate the toxicity of Abeta peptides, particularly in females, without significantly affecting Abeta accumulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
141
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1149-62
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16753269-Alzheimer Disease, pubmed-meshheading:16753269-Amyloid, pubmed-meshheading:16753269-Amyloid beta-Protein Precursor, pubmed-meshheading:16753269-Analysis of Variance, pubmed-meshheading:16753269-Animals, pubmed-meshheading:16753269-Behavior, Animal, pubmed-meshheading:16753269-Blotting, Western, pubmed-meshheading:16753269-Cognition Disorders, pubmed-meshheading:16753269-Cyclooxygenase 2, pubmed-meshheading:16753269-Cyclooxygenase Inhibitors, pubmed-meshheading:16753269-Disease Models, Animal, pubmed-meshheading:16753269-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:16753269-Exploratory Behavior, pubmed-meshheading:16753269-Female, pubmed-meshheading:16753269-Fluorescent Antibody Technique, pubmed-meshheading:16753269-Gene Expression, pubmed-meshheading:16753269-Male, pubmed-meshheading:16753269-Maze Learning, pubmed-meshheading:16753269-Membrane Proteins, pubmed-meshheading:16753269-Memory, Short-Term, pubmed-meshheading:16753269-Mice, pubmed-meshheading:16753269-Mice, Inbred C57BL, pubmed-meshheading:16753269-Mice, Transgenic, pubmed-meshheading:16753269-Presenilin-1, pubmed-meshheading:16753269-Pyrazoles, pubmed-meshheading:16753269-Sex Characteristics, pubmed-meshheading:16753269-Sulfonamides
pubmed:year
2006
pubmed:articleTitle
Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern.
pubmed:affiliation
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural