Preferential localization of prostamide/prostaglandin F synthase in myelin sheaths of the central nervous system

Prostaglandin (PG) F2α is a product of cyclooxygenase (COX)-catalyzed metabolism of arachidonic acid and exerts biological functions in various tissues. Prostaglandin ethanolamide (prostamide) F2α is a COX-2-catalyzed metabolite of arachidonoyl ethanolamide (anandamide) that induces pharmacological actions in ocular tissues. Although PGF2α is one of the most abundant prostaglandins in the brain, function of PGF2α in the central nervous system (CNS) has not been extensively investigated. Recently identified prostamide/PGF synthase catalyzes the reductions of prostamide H2 to prostamide F2α and PGH2 to PGF2α, chiefly in the CNS. We examined tissue distribution of the enzyme in the CNS by immunohistochemistry, double immunofluorescence, and immuno-electron microscopy. We confirmed histological findings by immunofluorescence analyses of brain cell cultures. Prostamide/PGF synthase was expressed preferentially in the white matter bundles of the entire CNS of adult mice with less marked expression in neuronal cell bodies. The enzyme was colocalized with myelin basic protein (MBP) in myelin sheaths but not in axons. At the ultrastructural level, the enzyme was localized to myelin sheaths. Expression of the enzyme increased between P9 and P14 during the postnatal development, presumably in accordance with myelinogenesis. Cultured oligodendrocytes at 7 days in vitro expressed the enzyme in cytoplasmic processes where the enzyme was colocalized with MBP. Immunoreactivity for COX-2 was detected in white matter and cultured oligodendrocytes. Relatively selective localization of prostamide/PGF synthase suggests that myelin sheaths of the CNS may serve as the sites for producing prostamide F2α and/or PGF2α, which may contribute to the formation and maintenance of central myelin.

Research Highlights►Prostamide/prostaglandin F synthase (PM/PGFS) is a relatively new CNS enzyme. ►We first determined the CNS distribution of PM/PGFS. ►PM/PGFS was preferentially localized in myelin sheaths of the entire CNS. ►Oligodendrocytes in culture expressed PM/PGFS.