کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2777892 1152772 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Time-dependent changes in the brain arachidonic acid cascade during cuprizone-induced demyelination and remyelination
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی بالینی
پیش نمایش صفحه اول مقاله
Time-dependent changes in the brain arachidonic acid cascade during cuprizone-induced demyelination and remyelination
چکیده انگلیسی

Phospholipases A2 (PLA2) are the enzymatic keys for the activation of the arachidonic acid (AA) cascade and the subsequent synthesis of pro-inflammatory prostanoids (prostaglandins and tromboxanes). Prostanoids play critical roles in the initiation and modulation of inflammation and their levels have been reported increased in several neurological and neurodegenerative disorders, including multiple sclerosis (MS).Here, we aimed to determine whether brain expression PLA2 enzymes and the terminal prostagland in levels are changed during cuprizone-induced demyelination and in the subsequent remyelination phase.Mice were given the neurotoxicant cuprizone through the diet for six weeks to induce brain demyelination. Then, cuprizone was withdrawn and mice were returned to a normal diet for 6 weeks to allow spontaneous remyelination.We found that after 4–6 weeks of cuprizone, sPLA2(V) and cPLA2, but not iPLA2(VI), gene expression was upregulated in the cortex, concomitant with an increase in the expression of astrocyte and microglia markers. Cyclooxygenase (COX)-2 gene expression was consistently upregulated during all the demyelination period, whereas COX-1 sporadically increased only at week 5 of cuprizone exposure. However, we found that at the protein level only sPLA2(V) and COX-1 were elevated during demyelination, with COX-1 selectively expressed by activated and infiltrated microglia/macrophages and astrocytes. Levels of PGE2, PGD2, PGI2 and TXB2 were also increased during demyelination. During remyelination, none of the PLA2 isoforms was significantly changed, whereas COX-1 and -2 were sporadically upregulated only at the gene expression level. PGE2, PGI2 and PGD2 levels returned to normal, whereas TXB2 was still upregulated after 3 weeks of cuprizone withdrawal.Our study characterizes for the first time time-dependent changes in the AA metabolic pathway during cuprizone-induced demyelination and the subsequent remyelination and suggests that sPLA2(V) is the major isoform contributing to AA release.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Prostaglandins, Leukotrienes and Essential Fatty Acids - Volume 85, Issue 1, July 2011, Pages 29–35
نویسندگان
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