Cuprizone induced-demyelination in mice alters brain expression of genes involved in arachidonic acid metabolism .
Year: 2009
Type: conference-paper
Abstract: Chronic feeding with the copper chelator cuprizone in mice \ncauses oligodendrocyte death and subsequent reversible \ndemyelination. Although the mechanism of demyelination is \nunknown, activation of glia is integral to the process. Since \nmetabolism of arachidonic acid (AA) is involved in glial \nactivation, we hypothesized that cuprizone exposure would \nalter expression of AA cascade genes. Mice were fed 0.2 % \ncuprizone in the diet for 6 weeks and then returned to a normal \ndiet. Histochemistry with the myelin stains Black Gold and \nFluoromyelin demonstrated that frank demyelination and \ninflux of glial cells into the corpus collosum begins at week 3 \nand peaks at week 5. A decrease in myelin and oligodendrocyte \nmarkers, accompanied by increased expression of markers of \nmicroglia (CD11b) and astrocytes (glial acidic fibrillary \nprotein), was evident at week one. Gene expression of \ncyclooxygenase-2 and 15-lipoxygenase (LOX) was also changed \nat week one, suggesting that these genes are either involved \nin or respond to early demyelination. Expression of 5-LOX was \nnot changed during early demyelination but it peaked during \nweek 5, when glial markers and frank demyelination also \nreached their peak, suggesting that 5-LOX expression is a \nconsequence of the massive influx of inflammatory cells into \nthe area of demyelination. Our study is the first to demonstrate \nthat multiple enzymes involved in arachidonic acid metabolism are altered in the cuprizone model of demyelination and \nremyelination. These data may help to develop new therapeutic \ntargets to treat human demyelinating diseases, such as multiple \nsclerosis. \nSupported by the Intramural Research Program of the NIH, \nNIA.
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2591901642