Abstract
In addition to regulating reproductive functions in the brain and periphery, estrogen has tropic and neuroprotective functions in the central nervous system (CNS). Estrogen administration has been demonstrated to provide protection in several animal models of CNS disorders, including stroke, brain injury, epilepsy, Parkinson's disease, Alzheimer's disease, age-related cognitive decline and multiple sclerosis. Here, we use a model of toxin-induced oligodendrocyte death which results in demyelination, reactive gliosis, recruitment of oligodendrocyte precursor cells and subsequent remyelination to study the potential benefit of 17beta-estradiol (E2) administration in male mice. The results indicate that E2 partially ameliorates loss of oligodendrocytes and demyelination in the corpus callosum. This protection is accompanied by a delay in microglia accumulation as well as reduced mRNA expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFalpha), and insulin-like growth factor-1 (IGF-1). E2 did not significantly alter the accumulation of astrocytes or oligodendrocyte precursor cells, or remyelination. These data obtained from a toxin-induced, T cell-independent model using male mice provide an expanded view of the beneficial effects of estrogen on oligodendrocyte and myelin preservation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens / metabolism
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Cell Count / methods
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Cuprizone / toxicity*
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Demyelinating Diseases* / chemically induced
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Demyelinating Diseases* / pathology
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Demyelinating Diseases* / prevention & control
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Disease Models, Animal
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Drug Interactions
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Estradiol / blood
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Estradiol / therapeutic use*
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Estrogens / therapeutic use*
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Gene Expression Regulation / drug effects
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Glial Fibrillary Acidic Protein / metabolism
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Glutathione Transferase / metabolism
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Indoles
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism
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Macrophages / drug effects
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Male
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Mice
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Mice, Inbred C57BL
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Microglia / drug effects
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Microglia / physiology
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Monoamine Oxidase Inhibitors / toxicity*
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Oligodendroglia / drug effects*
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Periodic Acid
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Plant Lectins
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Proteoglycans / metabolism
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Stem Cells / drug effects
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Stem Cells / physiology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antigens
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Estrogens
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Glial Fibrillary Acidic Protein
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Indoles
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Monoamine Oxidase Inhibitors
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Plant Lectins
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Proteoglycans
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Ricinus communis agglutinin-1
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Tumor Necrosis Factor-alpha
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chondroitin sulfate proteoglycan 4
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Periodic Acid
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Luxol Fast Blue MBS
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Estradiol
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Cuprizone
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Insulin-Like Growth Factor I
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Glutathione Transferase