Estrogen increases retrograde labeling of motoneurons: evidence of a nongenomic mechanism
Estrogen increases retrograde labeling of motoneurons: evidence of a nongenomic mechanism
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DOI：
10.1152/ajpcell.00542.2003
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发表时间：
2004-08-01
影响因子：
5.5
通讯作者：
Weidner, DA
中科院分区：
文献类型：
--
作者：
Murashov, AK;Islamov, RR;Weidner, DA
雌激素具有通过不同信号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，我们研究了直接应用于切断的坐骨神经的雌激素和 ERK 和 PI3K 抑制剂对腰椎运动神经元逆行标记的影响。将逆行示踪剂 (Fluorogold) 和 17β-雌二醇的混合物，与雌激素受体拮抗剂 ICI 182,780、ERK1/2 通路抑制剂 (U0126)、PI3K 抑制剂 (LY-294002) 或蛋白质合成抑制剂 (放线菌酮) 联合应用于横断的坐骨神经近端残端，持续 24 小时。 h.与单独使用 Fluorogold 相比，Fluorogold 与 17β-雌二醇的共同应用使逆行标记的腰椎运动神经元的数量显着增加。应用 ICI 182,780、U0126、LY-294002 和放线菌酮可抑制逆行标记的雌激素增强作用。挤压损伤后 24 小时，对坐骨神经进行免疫组织化学分析，结果显示磷酸化 ERK 在再生神经纤维中积累。数据表明雌激素、ERK、PI3K 和蛋白质合成在 Fluorogold 的摄取和逆行转运中发挥作用。我们认为雌激素在周围神经纤维中的作用是通过 ERK 和 PI3K 信号通路介导的，并且依赖于局部蛋白质合成。
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.