Prostaglandin F2α FP receptor inhibitor reduces demyelination and motor dysfunction in a cuprizone-induced multiple sclerosis mouse model.

Abstract

Previously, we have demonstrated that prostamide/PGF synthase, which catalyzes the reduction of prostaglandin (PG) H2 to PGF2α, is constitutively expressed in myelin sheaths and cultured oligodendrocytes, suggesting that PGF2α has functional significance in myelin-forming oligodendrocytes. To investigate the effects of PGF2α/FP receptor signaling on demyelination, we administrated FP receptor agonist and antagonist to cuprizone-exposed mice, a model of multiple sclerosis. Mice were fed a diet containing 0.2% cuprizone for 5 weeks, which induces severe demyelination, glial activation, proinflammatory cytokine expression, and motor dysfunction. Administration of the FP receptor antagonist AL-8810 attenuated cuprizone-induced demyelination, glial activation, and TNFα expression in the corpus callosum, and also improved the motor function. These data suggest that during cuprizone-induced demyelination, PGF2α/FP receptor signaling contributes to glial activation, neuroinflammation, and demyelination, resulting in motor dysfunction. Thus, FP receptor inhibition may be a useful symptomatic treatment in multiple sclerosis.

• Authors: K Iwasa, S Yamamoto, M Takahashi, S Suzuki, S Yagishita, T Awaji, K Maruyama, K Yoshikawa
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) Vol. 91 Issue 5 Pg. 175-82 (Nov 2014) ISSN: 1532-2823 [Electronic] Scotland
• PMID: 25224839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Prostaglandin
• Tumor Necrosis Factor-alpha
• prostaglandin F2alpha receptor
• AL 8810
• Prostaglandin H2
• Cuprizone
• Dinoprost

Topics

• Animals
• Corpus Callosum (drug effects, metabolism, pathology)
• Cuprizone (toxicity)
• Demyelinating Diseases (metabolism, pathology)
• Dinoprost (administration & dosage, analogs & derivatives)
• Disease Models, Animal
• Humans
• Mice
• Motor Activity (drug effects, genetics)
• Multiple Sclerosis (chemically induced, drug therapy, metabolism, pathology)
• Myelin Sheath (metabolism)
• Oligodendroglia (metabolism)
• Prostaglandin H2 (metabolism)
• Receptors, Prostaglandin (metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis)