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Estrogen increases retrograde labeling of motoneurons: evidence of a nongenomic mechanism.

机译:雌激素增加运动神经元的逆行标记:非基因组机制的证据。

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Estrogen has a variety of neurotrophic effects mediated via different signaling cascades, including ERK and phosphatidylinositol 3-kinase (PI3K) pathways. In this study, we investigated effects of estrogen and inhibitors for ERK and PI3K applied directly onto the cut sciatic nerve on retrograde labeling of lumbar motoneurons. A mix of retrograde tracer (Fluorogold) and 17beta-estradiol, in combination with an antagonist for estrogen receptors ICI 182,780, an inhibitor of ERK1/2 pathway (U0126), an inhibitor of PI3K (LY-294002), or a protein synthesis inhibitor (cycloheximide), was applied to the proximal stump of the transected sciatic nerve for 24 h. Coapplication of Fluorogold with 17beta-estradiol produced a significant increase in the number of retrograde-labeled lumbar motoneurons, compared with Fluorogold alone. Estrogen potentiation of retrograde labeling was inhibited by application of ICI 182,780, U0126, LY-294002, and cycloheximide. Immunohistochemical analysis of the sciatic nerve, 24 h following crush injury, revealed accumulation of phospho-ERK in regenerating nerve fibers. The data suggest a role for estrogen, ERK, PI3K, and protein synthesis in the uptake and retrograde transport of Fluorogold. We propose that estrogen action in peripheral nerve fibers is mediated via the ERK and PI3K signaling pathways and is reliant on local protein synthesis.
机译:雌激素具有通过不同的信号传导级联介导的多种神经营养作用,包括ERK和磷脂酰肌醇3-激酶(PI3K)途径。在这项研究中,我们研究了雌激素以及直接应用于坐骨神经切开的ERK和PI3K抑制剂对腰运动神经元逆行标记的作用。逆行示踪剂(Fluorogold)和17β-雌二醇的混合物,与雌激素受体拮抗剂ICI 182,780,ERK1 / 2途径抑制剂(U0126),PI3K抑制剂(LY-294002)或蛋白质合成抑制剂结合使用(环己酰亚胺)应用于坐骨神经切开的近端残端24 h。与单独的荧光金相比,荧光金与17β-雌二醇的共同应用显着增加了逆行标记的腰运动神经元的数量。应用ICI 182,780,U0126,LY-294002和环己酰亚胺可抑制逆行标记的雌激素增强作用。挤压伤后24小时对坐骨神经的免疫组织化学分析显示,磷酸-ERK积累在再生神经纤维中。数据表明雌激素,ERK,PI3K和蛋白质合成在荧光金的摄取和逆行运输中发挥作用。我们建议,雌激素在周围神经纤维中的作用是通过ERK和PI3K信号传导途径介导的,并且依赖于局部蛋白质的合成。

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