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Estrogen Therapy in a Viral Murine Model of Multiple Sclerosis

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dc.contributor.advisor Welsh, Christabel Jane R. en_US
dc.contributor.advisor Li, Jianrong en_US
dc.creator Gomez, Francisco Pascual en_US
dc.date.accessioned 2012-10-19T15:31:11Z en_US
dc.date.accessioned 2012-10-22T18:05:07Z
dc.date.available 2016-08-31 en_US
dc.date.created 2012-08 en_US
dc.date.issued 2012-10-19 en_US
dc.date.submitted August 2012 en_US
dc.identifier.uri http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11808 en_US
dc.description.abstract Multiple sclerosis (MS) is an idiopathic neurodegenerative, demyelinating disease of the central nervous system (CNS). MS affects females more than males (3:1) and pregnancy reduces the number of relapses especially during the third trimester when 17-beta-estradiol (E2) and estriol (E3) are at their highest levels. In order to study the role of estrogens as potential therapeutic agents for MS we investigated their role in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination (TVID). SJL female mice were infected intracranially with Theiler's virus or PBS. The mice in the treatment groups were clinically scored and at week 20 they were ovarectomized (OVx) and given a subdermal pellet containing either 1) 0.1mg of E2, 2) 5mg of E3, or 3) placebo. Four weeks after treatment initiation, the mice were sacrificed and tissue samples were collected and vertebral columns and brains were fixed and placed in paraffin for histological analysis using either hematoxylin and eosin (H&E) stain for general anatomic features or Weil's stain for myelin. No signs of clinical disease developed in any of the sham-infected mice. Prior to ovariectomy, infected mice had developed significant clinical scores indicative of demyelination. Mice in the placebo and E3-treatment groups deteriorated rapidly whereas the E2-treated mice improved significantly during the course of the treatment. Uteri were used to assess hormonal effects post-ovariectomy. Hormone treated groups were significantly different from placebo, indicating hormones were present. Hormone treatment showed significant differences among treatment groups for both inflammation and demyelination. E2-treatment significantly decreased inflammation compared to placebo and E3. E2 was also effective in reducing demyelination compared to placebo groups but not E3. E3 treatment was effective in reducing inflammation compared to placebo, but no significance was found for demyelination. Both E3 and E2 treated mice developed lower antibody levels against TMEV. The improvement in clinical signs, inflammation, demyelination, and the reduction of antibody levels in 17-beta-estradiol-treated mice indicate a therapeutic potential for the treatment of MS. en_US
dc.format.mimetype application/pdf en_US
dc.language.iso en_US en_US
dc.subject Multiple Sclerosis en_US
dc.subject Theiler's virus en_US
dc.subject TVID en_US
dc.subject Estrogens en_US
dc.subject Demyelination en_US
dc.subject Inflammation en_US
dc.title Estrogen Therapy in a Viral Murine Model of Multiple Sclerosis en_US
dc.type Thesis en
thesis.degree.department Veterinary Integrative Biosciences en_US
thesis.degree.discipline Biomedical Sciences en_US
thesis.degree.grantor Texas A&M University en_US
thesis.degree.name Master of Science en_US
thesis.degree.level Masters en_US
dc.contributor.committeeMember Sohrabji, Farida en_US
dc.contributor.committeeMember Storts, Ralph W. en_US
dc.type.genre thesis en_US
dc.type.material text en_US
local.embargo.terms 2016-08-31 en_US
local.embargo.lift 2016-08-31

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