17β-estradiol protects male mice from cuprizone-induced demyelination and oligodendrocyte loss

NEUROBIOLOGY OF DISEASE

卷:39

Article

Taylor, Lorelei C.^1,3  Puranam, Kasturi³  Gilmore, Wendy⁵  Ting, Jenny P-Y.^1,2,3  Matsushima, Glenn K.^1,2,3,4 

[1] Univ N Carolina, Curriculum Neurobiol, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Program Mol Biol & Biotechnol, Chapel Hill, NC 27599 USA

[5] Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA

关键词: Demyelination;    Myelin;    Cuprizone;    Estrogen;    E2;    17 beta-estradiol;    Oligodendrocyte;    Microglia;    TNF alpha;    Tumor necrosis factor alpha;   

DOI  :  10.1016/j.nbd.2010.03.016

来源: Elsevier

【 摘 要 】

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 17 beta-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 (TNF alpha), 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. (C) 2010 Elsevier Inc. All rights reserved.

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