title: The promyelinating properties of androstenediol in gliotoxin-induced demyelination in rat corpus callosum.
abstract: OBJECTIVE
  Experimental evidence has shown that the adrenal steroid hormone, androstenediol, dampens the symptoms of demyelination. However, the cellular and molecular effects of androstenediol are not yet known. In the present study, we investigated the cellular and subcellular effects of this hormone in a gliotoxin-induced demyelination model.
  
  
  METHODS
  Male Sprague Dawley rats received 2 μl of either saline or the gliotoxin ethidium bromide (EB, 0.04%) into the corpus callosum. These rats received daily subcutaneous injections of either oil or androstenediol (5 mg/kg). Their brains were collected at 2, 7, 14 and 28 days post-EB injection. Demyelinated lesions were assessed using Luxol fast blue staining. Immunofluorescent staining was used to investigate the number of oligodendrocyte progenitor cells, their maturation and microglial activation at the lesion site. Remyelination was further explored using transmission electron microscopy. The expression levels of total and phosphorylated MBP isoforms and CNPase were explored using western blot.
  
  
  RESULTS
  Androstenediol decreased the size of demyelinated lesions in the corpus callosum at 7 and 14 days post-EB injection. It enhanced the number of oligodendrocyte precursor cells, promoted an increase in the number of mature oligodendrocytes and reduced microglial activation. Androstenediol also stimulated the phosphorylation of MBP at the site of the lesion and promoted remyelination of the affected axons.
  
  
  CONCLUSIONS
  These data strongly suggest that androstenediol is endowed with promyelinating properties in a model of focal gliotoxin-induced demyelination. It induces its promyelinating effects by enhancing the number of oligodendrocyte precursor cells and their maturation at the lesion site.
authors: Department of Physiology, Faculty of Medicine, Kuwait University, Safat, Kuwait.
authors: Samah
authors: S
authors: Kalakh
authors: Department of Physiology, Faculty of Medicine, Kuwait University, Safat, Kuwait.
authors: Abdeslam
authors: A
authors: Mouihate
mesh_terms: D015114:Androstenediol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003337:Corpus Callosum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005912:Gliotoxin; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004676:Myelin Basic Protein; D005912:Gliotoxin; D015114:Androstenediol
keywords: corpus callosum; neurosteroids; oligodendrocyte precursor cells; phosphorylated myelin basic protein