Target regulation of neuronal plasticity

在确定在神经元调节中起重要作用的因素方面已经取得了相当大的进展 可塑性，无论是在发育过程中还是在成熟阶段。私隐专员公署一直积极研究其中一个例子。 可塑性，即成熟的交感神经轴突生长到受损的CMS中，使用体内和体内的各种方法 体外操作。子宫交感神经的反应是“自然”可塑性的一个戏剧性例子 循环中性激素水平的变化。子宫交感神经表现为恒定时相 在自然发情周期中的退化和再生，反映了循环水平的波动 雌激素。值得注意的是，在正常情况下，子宫交感神经末梢丛完全退化。 怀孕并在分娩后再生。这种“天然”可塑性的失败发生在病理性的 例如先兆子痫，这可能对母亲和胎儿都是致命的。前苏联的起因(S) 子痫尚不清楚，但持续的交感神经支配可能通过引起血管收缩而起作用。 在子宫肌瘤(肌瘤)的情况下，这是性激素敏感的良性子宫肌层肿瘤 在高达77%的育龄妇女中发生，交感神经缺失。事实上，子宫肌瘤类似于 自主神经缺失和细胞外浓缩的妊娠子宫肌层 矩阵(ECM)组件。子宫交感神经可塑性的机制还不完全清楚。 可以理解，但现有证据表明，这种可塑性反映了 靶标中的生长促进和生长抑制物质，以及激素诱导的 子宫投射交感神经元的感受性。初步研究表明，子宫底物- 结合的信号可能有助于子宫交感神经的可塑性。 建议是：(1)确定底物结合信号对细胞的“自然”可塑性的贡献 子宫交感神经支配；(B)探讨底物结合信号在交感神经调节中的作用 子痫前期和子宫肌瘤的神经支配；(3)评估性激素和子宫肌瘤的相互作用 神经营养因子与子宫底物结合的信号在神经调节中的作用。拟议的工作是一项 将主要在研究所开展的合作工作 在乌拉圭蒙得维的亚，Monica Brauer博士作为NIH#R01NS044972号赠款的延伸。

Considerable progress has been made in identifying factors that play important roles in regulating neuronal plasticity, both during development and in maturity. The PI has been actively studying one example of such plasticity, i.e., the growth of mature sympathetic axons into the injured CMS, using a variety of in vivo and in vitro manipulations. A dramatic example of "natural" plasticity is the response of uterine sympathetic nerves to changes in circulating levels of sex hormones. Uterine sympathetic nerves show constant phases of degeneration and regeneration during the natural estrous cycle, reflecting fluctuations in circulating levels of estrogen. Remarkably, the uterine sympathetic terminal plexus degenerates completely during normal pregnancy and regenerates after parturition. Failure of this "natural" plasticity occurs in pathological situations such as pre-eclampsia, which can be fatal to both mother and fetus. The cause(s) of pre- eclampsia are unknown, but persistent sympathetic innervation may contribute by inducing vasoconstriction. In the case of uterine leiomyomas (fibroids), which are sex hormone-sensitive benign myometrial tumors that occur in up to 77% of women of reproductive age, sympathetic nerves are absent. In fact, fibroids resemble the pregnant myometrium in both the absence of autonomic nerves and the enrichment of extracellular matrix (ECM) components. The mechanisms underlying plasticity in uterine sympathetic nerves are not fully understood, but available evidence indicates that such plasticity reflects changes in the balance between growth-promoting and growth-inhibiting substances in the target, as well as hormone-induced changes in the receptivity of uterine-projecting sympathetic neurons. Preliminary studies indicate that uterine substrate- bound signals are likely to contribute to plasticity in uterine sympathetic nerves.The goals of the present proposal are: (1) to establish the contribution of substrate-bound signals to the "natural" plasticity of the uterine sympathetic innervation; (b) to explore the role of substrate-bound signals in regulating sympathetic innervation in pre-eclampsia and uterine leiomyoma; (3) and to assess the interaction of sex hormones and neurotrophins with uterine substrate-bound signals in regulating innervation. The proposed work is a collaborative effort to be conducted primarily at the Institute de Investigaciones Biol6gicas Clemente Estable in Montevideo, Uruguay with Dr. Monica Brauer as an extension of NIH grant #R01NS044972.