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, Z. Berente, S. Komoly, Cordian Beyer

Research output: Contribution to journalArticle

121 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 - 2009

Fingerprint

Cuprizone
Corpus Callosum
Demyelinating Diseases
Progesterone
Estradiol
Hormones
Steroids
Oligodendroglia
Multiple Sclerosis
Estrogens
Brain
Gonadal Steroid Hormones
Insulin-Like Growth Factor I
Pregnant Women
Young Adult
Neck
Therapeutics
Magnetic Resonance Imaging
Clinical Trials
Staining and Labeling

Keywords

  • Estrogen
  • Hormones
  • Multiple sclerosis
  • Neuroprotection

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Acs, P., Kipp, M., Norkute, A., Johann, S., Clarner, T., Braun, A., ... Beyer, C. (2009). 17β-Estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice. GLIA, 57(8), 807-814. https://doi.org/10.1002/glia.20806

17β-Estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice. / Acs, Peter; Kipp, Markus; Norkute, Akvile; Johann, Sonja; Clarner, Tim; Braun, Alena; Berente, Z.; Komoly, S.; Beyer, Cordian.

In: GLIA, Vol. 57, No. 8, 2009, p. 807-814.

Research output: Contribution to journalArticle

Acs, P, Kipp, M, Norkute, A, Johann, S, Clarner, T, Braun, A, Berente, Z, Komoly, S & Beyer, C 2009, '17β-Estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice', GLIA, vol. 57, no. 8, pp. 807-814. https://doi.org/10.1002/glia.20806
Acs, Peter ; Kipp, Markus ; Norkute, Akvile ; Johann, Sonja ; Clarner, Tim ; Braun, Alena ; Berente, Z. ; Komoly, S. ; Beyer, Cordian. / 17β-Estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice. In: GLIA. 2009 ; Vol. 57, No. 8. pp. 807-814.
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