De novo synthesized estradiol protects against methylmercury-induced neurotoxicity in cultured rat hippocampal slices.
De novo synthesized estradiol protects against methylmercury-induced neurotoxicity in cultured rat hippocampal slices.
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DOI：
10.1371/journal.pone.0055559
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mukuda T
中科院分区：
文献类型：
--
作者：
Yamazaki T;Yamamoto M;Ishihara Y;Komatsu S;Munetsuna E;Onizaki M;Ishida A;Kawato S;Mukuda T
雌激素是一种女性性类固醇，具有神经保护作用。雌激素在大脑的特定区域合成。尽管脑内合成雌激素的神经保护作用的直接证据尚未得到明确证实，但从头合成的雌激素可能在脑内发挥保护作用。甲基汞（MeHg）是一种神经毒素，可导致中枢神经系统神经元变性。甲基汞的神经毒性具有区域特异性，其选择性神经毒性的分子机制尚未明确。本研究观察了17β-雌二醇对甲基汞所致大鼠海马神经毒性的保护作用。通过碘化丙啶荧光成像定量测定甲基汞对海马器官型切片培养物的神经毒性作用。用甲基汞处理切片24小时，以剂量依赖的方式引起细胞死亡。外源性雌二醇预处理可减轻甲基汞的毒性。切片重新合成雌二醇。雌二醇的合成不受1 µM甲基汞处理的影响。甲基汞的毒性可通过抑制雌二醇的合成而增强，而外源性雌二醇的加入可使甲基汞的毒性恢复。雌二醇的神经保护作用可被雌激素受体（ER）拮抗剂所抑制，并可被ERα和ERβ激动剂所模拟，表明其神经保护作用是由ER介导的。海马重新合成雌二醇通过ERα和ERβ介导的途径保护海马细胞免受甲基汞诱导的神经毒性。雌二醇的自我保护作用可能是脑对甲基汞毒性选择性敏感的机制之一。
Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined. Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs. Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity.
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影响因子：
4.8
作者：
Konkle, Anne T. M.;McCarthy, Margaret M.
通讯作者：
McCarthy, Margaret M.
影响因子：
3
作者：
MACKLIS, JD;MADISON, RD
通讯作者：
MADISON, RD
影响因子：
4.7
作者：
Falluel-Morel, Anthony;Sokolowski, Katie;DiCicco-Bloom, Emanuel
通讯作者：
DiCicco-Bloom, Emanuel
DOI：
10.1073/pnas.2630225100
发表时间：
2004-01-20
影响因子：
11.1
作者：
Hojo, Y;Hattori, T;Kawato, S
通讯作者：
Kawato, S
影响因子：
4.8
作者：
Munetsuna, Eiji;Hojo, Yasushi;Yamazaki, Takeshi
通讯作者：
Yamazaki, Takeshi