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Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis

MacKenzie-Graham, Allan J. and Rinek, Gilda A. and Avedisian, Andrea and Morales, Laurie B. and Umeda, Elizabeth and Boulat, Benoit and Jacobs, Russell E. and Toga, Arthur W. and Voskuhl, Rhonda R. (2012) Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis. Journal of Neuroscience Research, 90 (7). pp. 1310-1323. ISSN 0360-4012. PMCID PMC3350614. https://resolver.caltech.edu/CaltechAUTHORS:20120601-162834059

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Abstract

Gray matter atrophy is an important correlate to clinical disability in multiple sclerosis (MS), and many treatment trials include atrophy as an outcome measure. Atrophy has been shown to occur in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. The clinical severity of EAE is reduced in estrogen-reated mice, but it remains unknown whether estrogen treatment can reduce gray matter atrophy in EAE. In this study, mice with EAE were treated with either estrogen receptor (ER)-α ligand or ER-β ligand, and diffusion tensor images (DTI) were collected and neuropathology was performed. DTI showed atrophy in the cerebellar gray matter of vehicle-treated EAE mice compared with healthy controls but not in ER-α or ER-β ligand-treated EAE mice. Neuropathology demonstrated that Purkinje cell numbers were decreased in vehicle-treated EAE mice, whereas neither ER ligand-treated EAE groups showed a decrease. This is the first report of a neuroprotective therapy in EAE that unambiguously prevents gray matter atrophy while sparing a major neuronal cell type. Fractional anisotropy (FA) in the cerebellar white matter was decreased in vehicle- and ER-β ligand-treated but not in ER-α ligand-treated EAE mice. Inflammatory cell infiltration was increased in vehicle- and ER-β ligand-treated but not in ER-α ligand-treated EAE mice. Myelin staining was decreased in vehicle-treated EAE mice and was spared in both ER ligand-treated groups. This is consistent with decreased FA as a potential biomarker for inflammation rather than myelination or axonal damage in the cerebellum in EAE.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/jnr.23019DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/jnr.23019/abstractPublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350614/PubMed CentralArticle
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2012 Wiley Periodicals, Inc. Published online 13 March 2012 in Wiley Online Library. National Multiple Sclerosis Society; Contract grant number: FG 1759A1/1 (to A.M.G.); Contract grant number: RG 4033; Contract grant number: RG 4364; Contract grant number: CA 1028 (to R.R.V.); Contract grant sponsor: National Institutes of Health; Contract grant number: P41 RR013642 (to A.W.T.); Contract grant number: K24 NS062117 (to R.R.V.); Contract grant sponsor: National Institute of Biomedical Imaging and Bioengineering; Contract grant number: R01 EB000993 (to R.E.J.); Contract grant sponsor: Skirball Foundation (to R.R.V.); Contract grant sponsor: Hilton Foundation (to R.R.V.); Contract grant sponsor: Sherak Family Foundation (to R.R.V.).
Funders:
Funding AgencyGrant Number
National Multiple Sclerosis SocietyFG 1759A1/1
National Multiple Sclerosis SocietyRG 4033
National Multiple Sclerosis SocietyRG 4364
National Multiple Sclerosis SocietyCA 1028
NIHK24 NS062117
National Institute of Biomedical Imaging and BioengineeringR01 EB000993
Skirball FoundationUNSPECIFIED
Hilton FoundationUNSPECIFIED
Sherak Family FoundationUNSPECIFIED
Subject Keywords:DTI; multiple sclerosis; mouse; ligand
Issue or Number:7
PubMed Central ID:PMC3350614
Record Number:CaltechAUTHORS:20120601-162834059
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120601-162834059
Official Citation:MacKenzie-Graham, A. J., Rinek, G. A., Avedisian, A., Morales, L. B., Umeda, E., Boulat, B., Jacobs, R. E., Toga, A. W. and Voskuhl, R. R. (2012), Estrogen treatment prevents gray matter atrophy in experimental autoimmune encephalomyelitis. J. Neurosci. Res., 90: 1310–1323. doi: 10.1002/jnr.23019
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:31781
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:04 Jun 2012 21:45
Last Modified:03 Oct 2019 03:54

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