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Cited by 23Multiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration MechanismsEstrogen and related hormone effects

The DOI matches its Crossref record.

Castration of male C57L/J mice increases susceptibility and estrogen treatment restores resistance to Theiler's virus‐induced demyelinating disease

Fuller, Alyson, Yahikozawa, Hiroyuki, So, Eui Young, Dal Canto, Mauro, Koh, Chang‐Sung, Welsh, C. Jane, Kim, Byung S.·2007·Journal of Neuroscience Research
DOI 10.1002/jnr.21184
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Abstract

Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in immune‐mediated demyelination in selective mouse strains. We have previously demonstrated that the males of C57L mice are significantly more susceptible to TMEV‐induced demyelinating disease. To assess further the hormonal influence for this gender‐associated differential susceptibility, estrogen‐treated, castrated C57L mice were infected with TMEV and compared with sham‐operated and/or placebo‐treated mice. Interestingly, castration further elevated the susceptibility to virally induced demyelinating disease compared with sham‐castrated control mice, and prolonged treatment of castrated mice with estrogen restored the resistance to the level of control mice. These results strongly suggest that sex hormone levels contribute to the gender‐biased susceptibility to TMEV‐induced demyelinating disease. Mice treated with estrogen showed a significantly decreased level of virus‐specific Th1 responses both in the periphery and in the CNS. In addition, in vitro estrogen treatment was able to inhibit viral replication directly in macrophages, consistent with the lower level of viral RNA in microglia/macrophages in the CNS from castrated estrogen‐treated mice compared with controls. Also, estrogen treatment inhibited VCAM‐1 expression induced by tumor necrosis factor‐α in cerebral vascular endothelial (CVE) cells via inhibition of nuclear factor‐κB (NFκB), which is produced in various glial cells upon TMEV infection. Overall, estrogen treatment appears to exert its effects on viral replication, induction of immune responses, as well as infiltration of activated immune cells into the CNS via inhibition of NFκB function. © 2007 Wiley‐Liss, Inc.

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Metadata

Authors
Fuller, A., Yahikozawa, H., So, E. Y., Dal Canto, M., Koh, C., Welsh, C. J., & Kim, B. S.
Affiliations
  • Northwestern University (US)
  • Shinshu University (JP)
  • Texas A&M University (US)
Corresponding author
Kim, Byung S.
ORCID
Venue
Journal of Neuroscience Research
Publisher
Wiley
Published
2007-01-25
Volume
85
Issue
4
Pages
871-881
ISSN
  • 0360-4012 (ISSN-L)
  • 1097-4547
DOI
10.1002/jnr.21184
OpenAlex
W2091832684
Cited by
23
References
0
Citations by year
2026: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
FWCI
2.13
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neuroscience Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS-33008, R01NS033008, R01NS028752, NS-23349, NS-28752, P01NS023349)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords
Theiler's murine encephalomyelitis virus, castration, estrogen therapy, sex hormones, demyelination, Th1 response, microglia, VCAM-1, NF-κB, TNF-α, immune cell infiltration, viral encephalitis
MeSH terms
Animals, Antigen-Presenting Cells, Castration, Demyelinating Diseases, Disease Models, Animal, Disease Susceptibility, Estrogens, Flow Cytometry, Male, Mice, Inbred C57BL, T-Lymphocytes, Time Factors, Gene Expression, Cytokines, Theilovirus, Reverse Transcriptase Polymerase Chain Reaction, Endothelial Cells, Cell Proliferation, Mice

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