| Neuroprotective and anti-inflammatory effects of estrogen receptor ligand treatment in mice. | |
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MedLine Citation:
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PMID: 19442988 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Demyelination and neurodegeneration is a major contributor in the progression of disability in multiple sclerosis (MS). Thus, the development of therapies that are neuroprotective has elicited considerable interests. Estrogens and estrogen receptor (ER) ligand treatments are promising treatments to prevent MS-induced neurodegeneration and a multicenter phase II clinical trial of estriol as a beneficial therapy in MS is underway. Here, we discuss studies performed in our laboratory that examined the effects of ER ligands in the inflammatory/demyelinating disorder experimental autoimmune encephalomyelitis (EAE), a model of MS. Administration of estriol or 17beta-estradiol reduced clinical severity and this clinical disease improvement was associated with favorable changes in cytokine production. There was a significant decrease of neuronal pathology in gray matter along with myelin and axon preservation in white matter of spinal cords of mice with EAE. In subsequent experiments, we contrasted the results of ERalpha versus ERbeta ligand treatment. While ERalpha ligand treatment was anti-inflammatory, ERbeta ligand treatment was not. ERbeta ligand treatment nevertheless reduced demyelination and preserved axon numbers in white matter and prevented neuronal abnormalities in gray matter. Clinically, ERalpha ligand treatment abrogated the disease at the onset, while ERbeta ligand treatment had no effect at disease onset, but promoted recovery. Thus, unlike ERalpha ligand treatment, ERbeta ligand treatment was protective at the level of the target organ, independent of anti-inflammatory effects in the peripheral immune system. ERbeta ligand treatment should be considered as a potential neuroprotective agent for MS and other neurodegenerative diseases, particularly since breast and uterine cancer are mediated through ERalpha. |
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Authors:
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Seema Tiwari-Woodruff; Rhonda R Voskuhl |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-13 |
Journal Detail:
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Title: Journal of the neurological sciences Volume: 286 ISSN: 1878-5883 ISO Abbreviation: J. Neurol. Sci. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-12 Completed Date: 2009-12-17 Revised Date: 2011-01-26 |
Medline Journal Info:
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Nlm Unique ID: 0375403 Medline TA: J Neurol Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 81-5 Citation Subset: IM |
Affiliation:
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Department of Neurology, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. seemaw@ucla.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental / complications*, drug therapy, genetics, metabolism Estradiol / therapeutic use Estrogen Receptor alpha / deficiency, metabolism Estrogen Receptor beta / deficiency, metabolism Estrogens / therapeutic use* Ligands Mice Mice, Inbred C57BL Mice, Knockout Motor Activity / drug effects Myelin Proteins / metabolism Myelitis / etiology, prevention & control* Nerve Tissue Proteins / metabolism Neurodegenerative Diseases / etiology, prevention & control* Neuroprotective Agents / therapeutic use* Receptors, Estrogen |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS045443-01/NS/NINDS NIH HHS; R01 NS045443-04/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Estrogen Receptor alpha; 0/Estrogen Receptor beta; 0/Estrogens; 0/Ligands; 0/Myelin Proteins; 0/Nerve Tissue Proteins; 0/Neuroprotective Agents; 0/Receptors, Estrogen; 50-28-2/Estradiol |
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