Estrogen receptor-beta ligand treatment after disease onset is neuroprotective in the multiple sclerosis model

摘要

Multiple Sclerosis (MS) is an autoimmune disease characterized by inflammation and neurodegeneration. Current MS treatments were designed to reduce inflammation in MS, rather than to directly 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-beta (ERβ) ligand is known to effectively ameliorate clinical disease and provide neuroprotection in EAE. However, the protective effects of this ERβ ligand have only been demonstrated 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 as compared to vehicle treated animals. We observed no difference in the number of T lymphocytes, macrophages, or microglia in the CNS of vehicle versus 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.