title: Attenuation of corpus callosum axon myelination and remyelination in the absence of circulating sex hormones.
abstract: Sex differences in the structure and organization of the corpus callosum (CC) can be attributed to genetic, hormonal or environmental effects, or a combination of these factors. To address the role of gonadal hormones on axon myelination, functional axon conduction and immunohistochemistry analysis of the CC in intact, gonadectomized and hormone-replaced gonadectomized animals were used. These groups were subjected to cuprizone diet-induced demyelination followed by remyelination. The myelinated component of callosal compound action potential was significantly decreased in ovariectomized and castrated animals under normal myelinating condition. Compared to gonadally intact cohorts, both gonadectomized groups displayed more severe demyelination and inhibited remyelination. Castration in males was more deleterious than ovariectomy in females. Callosal conduction in estradiol-supplemented ovariectomized females was significantly increased during normal myelination, less attenuated during demyelination, and increased beyond placebo-treated ovariectomized or intact female levels during remyelination. In castrated males, the non-aromatizing steroid dihydrotestosterone was less efficient than testosterone and estradiol in restoring normal myelination/axon conduction and remyelination to levels of intact males. Furthermore, in both sexes, estradiol supplementation in gonadectomized groups increased the number of oligodendrocytes. These studies suggest an essential role of estradiol to promote efficient CC myelination and axon conduction in both sexes.
authors: Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles, CA 90095-1769, USA.
authors: Rhusheet
authors: R
authors: Patel
authors: Spencer
authors: S
authors: Moore
authors: Daniel K
authors: DK
authors: Crawford
authors: Gemmy
authors: G
authors: Hannsun
authors: Manda V
authors: MV
authors: Sasidhar
authors: Kevin
authors: K
authors: Tan
authors: Donna
authors: D
authors: Molaie
authors: Seema K
authors: SK
authors: Tiwari-Woodruff
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002369:Castration; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000097:blood* / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism / Q000648:ultrastructure; D012739:Gonadal Steroid Hormones / Q000097:blood*; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012739:Gonadal Steroid Hormones; D008996:Monoamine Oxidase Inhibitors; D018991:Myelin Proteolipid Protein; C047516:Plp1 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004958:Estradiol; D003471:Cuprizone