Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 121 (3), 418-27

The cyclooxygenase-2 Pathway via the PGE₂ EP2 Receptor Contributes to Oligodendrocytes Apoptosis in Cuprizone-Induced Demyelination

Affiliations

The cyclooxygenase-2 Pathway via the PGE₂ EP2 Receptor Contributes to Oligodendrocytes Apoptosis in Cuprizone-Induced Demyelination

Sara Palumbo et al. J Neurochem.

Abstract

Cyclooxygenases (COX)-1 and -2 are key enzymes required for the conversion of arachidonic acid to eicosanoids, potent mediators of inflammation. In patients with multiple sclerosis, COX-2 derived prostaglandins (PGs) are elevated in the CSF and COX-2 is up-regulated 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 multiple sclerosis.

Figures

Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Figure 5
Figure 5
Figure 6
Figure 6

Similar articles

See all similar articles

Cited by 14 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback