The cyclooxygenase-2 pathway via the PGE2 EP2 receptor contributes to oligodendrocytes apoptosis in cuprizone-induced demyelination
| Autor: | Palumbo, Sara, Toscano, Christopher D., Parente, Laura, Weigert, Roberto, Bosetti, Francesca |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
EP2 Subtype
Male Knockout Xanthones arachidonic acid cuprizone cyclooxygenases demyelination EP2 myelin Animals Apoptosis Caspase 3 Cattle Celecoxib Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Demyelinating Diseases Dinoprostone Fluorescent Antibody Technique Immunohistochemistry Mice Mice Inbred C57BL Mice Knockout Myelin Sheath Oligodendroglia Postural Balance Pyrazoles Real-Time Polymerase Chain Reaction Receptors Prostaglandin E EP2 Subtype Signal Transduction Sulfonamides Chelating Agents Cuprizone Biochemistry Cellular and Molecular Neuroscience Inbred C57BL Article Receptors Prostaglandin E lipids (amino acids peptides and proteins) |
| Popis: | Cyclooxygenases (COX)-1 and -2 are key enzymes required for the conversion of arachidonic acid (AA) to eicosanoids, potent mediators of inflammation. In patients with multiple sclerosis (MS), COX-2 derived prostaglandins (PGs) are elevated in the cerebrospinal fluid and COX-2 is upregulated in demyelinating plaques. However, it is not known whether COX-2 activity contributes to oligodendrocyte death. In cuprizone-induced demyelination, oligodendrocyte apoptosis and a concomitant increase in the gene expression of COX-2 and PGE2-EP2 receptor precede histological demyelination. COX-2 and EP2 receptor were expressed by oligodendrocytes, suggesting a causative role for the COX-2/EP2 pathway in the initiation of oligodendrocyte death and demyelination. COX-2 gene deletion, chronic treatment with the COX-2 selective inhibitor celecoxib, or with the EP2 receptor antagonist AH6809 reduced cuprizone-induced oligodendrocyte apoptosis, the degree of demyelination and motor dysfunction. These data indicate that the PGE2 EP2 receptor contributes to oligodendrocyte apoptosis and open possible new therapeutic approaches for MS. |
| Databáze: | OpenAIRE |
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