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. doi:10.1002/jnr.23019. 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.
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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.). | ||||||||||||||||||||
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Subject Keywords: | DTI; multiple sclerosis; mouse; ligand | ||||||||||||||||||||
Issue or Number: | 7 | ||||||||||||||||||||
PubMed Central ID: | PMC3350614 | ||||||||||||||||||||
DOI: | 10.1002/jnr.23019 | ||||||||||||||||||||
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: | 09 Nov 2021 20:00 |
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