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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yoon, Jaehee Winchester, Zachary Yasui, Norio Tiwari-woodruff, Seema Kaushalya Martinez-torres, Leonardo Kumar, Shalini Khalaj, Anna J. Yoo, Timothy Katzenellenbogen, John A. Moore, Spencer M. |
| Description | Author Affiliation: Moore SM ( Department of Neurology.); Khalaj AJ ( Department of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521); Kumar S ( Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience at the School of Medicine, University of California, Los Angeles, CA 90095); Winchester Z ( Department of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521); Yoon J ( Department of Neurology.); Yoo T ( Department of Neurology.); Martinez-Torres L ( Department of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521); Yasui N ( Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.); Katzenellenbogen JA ( Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.); Tiwari-Woodruff SK ( Department of Neurology, Division of Biomedical Sciences at the School of Medicine, University of California, Riverside, CA 92521); |
| Abstract | Currently available immunomodulatory therapies do not stop the pathogenesis underlying multiple sclerosis (MS) and are only partially effective in preventing the onset of permanent disability in patients with MS. Identifying a drug that stimulates endogenous remyelination and/or minimizes axonal degeneration would reduce the rate and degree of disease progression. Here, the effects of the highly selective estrogen receptor (ER) ß agonist indazole chloride (Ind-Cl) on functional remyelination in chronic experimental autoimmune encephalomyelitis (EAE) mice were investigated by assessing pathologic, functional, and behavioral consequences of both prophylactic and therapeutic (peak EAE) treatment with Ind-Cl. Peripheral cytokines from autoantigen-stimulated splenocytes were measured, and central nervous system infiltration by immune cells, axon health, and myelination were assessed by immunohistochemistry and electron microscopy. Therapeutic Ind-Cl improved clinical disease and rotorod performance and also decreased peripheral Th1 cytokines and reactive astrocytes, activated microglia, and T cells in brains of EAE mice. Increased callosal myelination and mature oligodendrocytes correlated with improved callosal conduction and refractoriness. Therapeutic Ind-Cl-induced remyelination was independent of its effects on the immune system, as Ind-Cl increased remyelination within the cuprizone diet-induced demyelinating model. We conclude that Ind-Cl is a refined pharmacologic agent capable of stimulating functionally relevant endogenous myelination, with important implications for progressive MS treatment. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Encephalomyelitis, Autoimmune, Experimental Drug Therapy Estrogen Receptor Beta Agonists Hydrocarbons, Chlorinated Pharmacology Immunologic Factors Indazoles Myelin Sheath Drug Effects Analysis Of Variance Animals Blotting, Western Chemistry Immunohistochemistry Therapeutic Use Mice Mice, Inbred C57BL Motor Skills Physiology Rotarod Performance Test Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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