17β-Estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice

Peter Acs, Markus Kipp, Akvile Norkute, Sonja Johann, Tim Clarner, Alena Braun, Zoltan Berente, Samuel Komoly, Cordian Beyer

Research output: Contribution to journalArticle

127 Citations (Scopus)

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 17β-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-α-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.

Original languageEnglish
Pages (from-to)807-814
Number of pages8
JournalGlia
Volume57
Issue number8
DOIs
Publication statusPublished - Sep 8 2009

Keywords

  • Estrogen
  • Hormones
  • Multiple sclerosis
  • Neuroprotection

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of '17β-Estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice'. Together they form a unique fingerprint.

  • Cite this