Target regulation of neuronal plasticity

神经元可塑性的目标调节

• 批准号: 7545537
• 负责人: David Brent Pettigrew
• 金额: $ 3.79万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-20 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545537
• 关键词: Accounting; Address; Adult; Affect; Age; Atrophic; Autonomic nervous system; Axon; Benign; Binding; Birth; Development; Environment; Equilibrium; Estrogens; Estrous Cycle; Evaluation; Extracellular Matrix; Failure; Fetus; Fibroid Tumor; Goals; Gonadal Steroid Hormones; Grant; Growth; Hormones; Human; In Vitro; Institutes; Knowledge; Laboratories; Methods; Mothers; Myelin; Myometrial; Natural regeneration; Nerve; Nerve Degeneration; Neurites; Neuronal Plasticity; Neurons; Pathology; Phase; Physiological; Play; Pre-Eclampsia; Pregnancy; Pregnant Uterus; Puberty; Recording of previous events; Regulation; Role; Signal Transduction; Tissues; Transgenic Mice; United States National Institutes of Health; Uruguay; Uterine Fibroids; Uterus; Woman; Work; autonomic nerve; axon growth; design; in vivo; inhibitor/antagonist; injured; myometrium; nerve supply; neurotrophic factor; parent grant; pregnant; reproductive; response; transcriptional coactivator p75; tumor; uterine receptivity; vasoconstriction; white matter

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.

在确定在调节神经元中起重要作用的因素方面取得了长足的进步 在发育和成熟度期间，可塑性。 PI一直在积极研究这样的例子 可塑性，即使用各种体内和在 体外操作。 “自然”可塑性的戏剧性例子是子宫交感神经的反应 发生性激素循环水平的变化。子宫交感神经显示 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，子宫交感末端神经丛在正常情况下完全退化 分娩后怀孕和再生。这种“自然”可塑性的失败发生在病理中 诸如先兆子痫之类的情况，对母亲和胎儿都可能致命。前的原因 子痫是未知的，但是持续的同情神经可能通过引起血管收缩而造成贡献。 对于子宫平滑肌瘤（肌瘤），是性激素敏感的良好肌层肿瘤 在多达77％的生殖年龄妇女中发生，不存在交感神经。实际上，肌瘤类似于 在缺乏自主神经和细胞外的富集的情况下，怀孕的子宫骨术 矩阵（ECM）组件。子宫交感神经中可塑性的基础机制尚未完全 理解，但可用的证据表明，这种可塑性反映了 目标中的促进生长和抑制生长的物质，以及激素诱导的变化 子宫预测的交感神经元的接受能力。初步研究表明子宫底物 绑定的信号可能有助于子宫交感神经中的可塑性。 提案是：（1）建立底物结合信号的贡献 子宫交感神经神经； （b）探索基材结合信号在调节同情心中的作用 子宫前和子宫平滑肌瘤的神经； （3）并评估性激素的相互作用和 具有子宫基质结合信号的神经营养蛋白在调节神经上。拟议的工作是 合作努力主要是在研究所biol6gicas Clemente估算的研究所进行的 在Montevideo，乌拉圭与莫妮卡·布劳尔（Monica Brauer）博士一起作为NIH授予＃R01NS044972的扩展。