title: The effect of omega-3 fatty acids on central nervous system remyelination in fat-1 mice.
abstract: There is a large body of experimental evidence suggesting that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are capable of modulating immune function. Some studies have shown that these PUFAs might have a beneficial effect in patients suffering form multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). This could be due to increased n-3 PUFA-derived anti-inflammatory lipid mediators. In the present study we tested the effect of an endogenously increased n-3 PUFA status on cuprizone-induced CNS demyelination and remyelination in fat-1 mice versus their wild-type (wt) littermates. Fat-1 mice express an n-3 desaturase, which allows them to convert n-6 PUFAs into n-3 PUFAs.
  
  
  
  CNS lipid profiles in fat-1 mice showed a significant increase of eicosapentaenoic acid (EPA) levels but similar docosahexaenoic acid levels compared to wt littermates. This was also reflected in significantly higher levels of monohydroxy EPA metabolites such as 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 brain tissue. Feeding fat-1 mice and wt littermates 0.2% cuprizone for 5 weeks caused a similar degree of CNS demyelination in both groups; remyelination was increased in the fat-1 group after a recovery period of 2 weeks. However, at p = 0.07 this difference missed statistical significance.
  
  
  
  These results indicate that n-3 PUFAs might have a role in promotion of remyelination after toxic injury to CNS oligodendrocytes. This might occur either via modulation of the immune system or via a direct effect on oligodendrocytes or neurons through EPA-derived lipid metabolites such as 18-HEPE.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Charité - Universitaetsmedizin Berlin, Campus Virchow Hospital, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Elise
authors.initials: E
authors.lastname: Siegert
authors.affiliation: Experimental and Clinical Research Center, Charité - Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.|NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité - Universitaetsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Lipdomix GmbH, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rothe
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Charité - Universitaetsmedizin Berlin, Campus Virchow Hospital, Augustenburger Platz 1, 13353, Berlin, Germany. karsten.weylandt@charite.de.|Experimental and Clinical Research Center, Charité - Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany. karsten.weylandt@charite.de.
authors.forename: Karsten H
authors.initials: KH
authors.lastname: Weylandt
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005260:Female; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology
chemical_list: D015820:Cadherins; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; C502406:fat1 protein, mouse; D004281:Docosahexaenoic Acids; D003471:Cuprizone; D015118:Eicosapentaenoic Acid
keywords: Inflammation; Lipid mediators; Multiple sclerosis; Oligodendrocytes; Remyelination; n-3 PUFAs