title: 17beta-estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice.
abstract: Sex hormones, for example, estrogen and progesterone, are thought to affect and delay progression of multiple sclerosis (MS) in pregnant women. Although both steroid hormones are neuroprotective in the brain and elevated during pregnancy, only estrogen was tested in clinical trials. To evaluate the role of 17beta-estradiol (E) and progesterone (P) in prevention demyelination, young adult male mice were fed with cuprizone for a defined time interval and simultaneously treated with steroids by repeated injections into the neck region. The status of myelination was analyzed by magnetic resonance imaging and conventional histological staining. The individual application of E and P resulted only in a moderate prevention of demyelination in the corpus callosum (CC). The combined treatment with both steroid hormones counteracted the process of demyelination. Expression of the mature (PLP and MBP) and premature (PDGF-alpha-R) oligodendrocyte markers were significantly increased after hormone application in the affected CC. In addition, both hormones stimulated astrogliosis and the expression of IGF-1. Microglial invasion in demyelinated CC was pronounced and additionally localized in the midline of CC after hormone treatment. These data show that sex steroids can protect the brain from demyelination and stimulate remyelination. It appears that only the administration of both hormones is fully effective. The beneficial steroid effect requires interactions with oligodendrocytes possibly by preventing their degeneration or recruitment from precursor cells which are stimulated to remyelinated fibers. The positive hormonal influence on myelination in the CNS may be a future therapeutically strategy for the treatment of MS.
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Pécs, Rét u. 2, Pécs, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Acs
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.forename: Akvile
authors.initials: A
authors.lastname: Norkute
authors.forename: Sonja
authors.initials: S
authors.lastname: Johann
authors.forename: Tim
authors.initials: T
authors.lastname: Clarner
authors.forename: Alena
authors.initials: A
authors.lastname: Braun
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Berente
authors.forename: Samuel
authors.initials: S
authors.lastname: Komoly
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003471:Cuprizone; D003599:Cytoskeleton / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism
chemical_list: D004967:Estrogens; D005904:Glial Fibrillary Acidic Protein; D009185:Myelin Proteins; D011374:Progesterone; D004958:Estradiol; D003471:Cuprizone; D007334:Insulin-Like Growth Factor I; D020796:Receptor, Platelet-Derived Growth Factor alpha