title: Estrogen receptor-β ligand treatment after disease onset is neuroprotective in the multiple sclerosis model.
abstract: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and neurodegeneration. Current MS treatments were designed to reduce inflammation in MS rather than directly to prevent neurodegeneration. Estrogen has well-documented neuroprotective effects in a variety of disorders of the CNS, including experimental autoimmune encephalomyelitis (EAE), the most widely used mouse model of MS. Treatment with an estrogen receptor-β (ERβ) ligand is known to ameliorate clinical disease effectively and provide neuroprotection in EAE. However, the protective effects of this ERβ ligand have been demonstrated only when administered prior to disease (prophylactically). Here we tested whether ERβ ligand treatment could provide clinical protection when treatment was initiated after onset of disease (therapeutically). We found that therapeutic treatment effectively ameliorated clinical disease in EAE. Specifically, ERβ ligand-treated animals exhibited preserved axons and myelin compared with vehicle-treated animals. We observed no difference in the number of T lymphocytes, macrophages, or microglia in the CNS of vehicle- vs. ERβ ligand-treated animals. Our findings show that therapeutically administered ERβ ligand successfully treats clinical EAE, bearing translational relevance to MS as a candidate neuroprotective agent.
authors: UCLA Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles, California 90095, USA.
authors: Amy J
authors: AJ
authors: Wisdom
authors: Yuan
authors: Y
authors: Cao
authors: Noriko
authors: N
authors: Itoh
authors: Rory D
authors: RD
authors: Spence
authors: Rhonda R
authors: RR
authors: Voskuhl
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D003711:Demyelinating Diseases / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000276:immunology; D011422:Propionates / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000819:agonists*; D012720:Severity of Illness Index
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D063308:Myelin-Oligodendrocyte Glycoprotein; D018696:Neuroprotective Agents; D009570:Nitriles; D010446:Peptide Fragments; D011422:Propionates; D011960:Receptors, Estrogen; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant
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