ESTROGEN IN THE AGING HYPOTHALAMUS

描述：（改编自应用程序）。雌激素对 雌性大鼠老化下丘脑中的突触连接可能 通过调节神经调节蛋白（GAP-43）的表达。雌激素 在雌性的一生中调节生殖活动 动物，并参与神经突生长过程中的发展，发病 卵巢周期、卵巢周期规律性和突触重塑 在下丘脑恒定和高剂量的雌二醇 给予雌性大鼠导致恒定的阴道发情，年龄- 在生殖衰老的相关阶段，卵巢 无排卵，很少甾体激素分泌， 停止。据观察，增加和减少， 从青春期前雌性大鼠中分离的特异性蛋白质的浓度 给予雌激素。其中一种分离的蛋白质显示出 表达水平显著增加，生物化学相似 神经调节素，GAP-43（kDa=4.3; pI=5.4）。神经调节素存在于 发育中的大鼠神经系统，在再生的神经突生长中， 神经元，并已被证明参与神经元的可塑性 在海马区。最近的研究表明，GAP-43 在类固醇致敏的动物中表达增加。迄今为止 雌激素影响突触连接的机制尚不清楚。 我们认为雌激素通过以下途径促进这种发生： 神经调素的调节，因为神经调素在细胞中高度表达 轴突在轴突生长发育和再生过程中。我们 建议确定衰老或雌激素是否调节了 衰老下丘脑中的突触连接和GAP-43表达。 我们的目标是确定突触连接的任何变化， 衰老雌性大鼠的下丘脑，其可能代表 卵巢周期和阴道上皮的变化， 与雌激素调节GAP-43表达相关的变化 老化的下丘脑神经元。研究将在性方面进行 成年（3 - 5个月）和更大（8 - 10个月）雌性 用雌激素或溶剂预处理的卵巢切除Sprague道利大鼠 48小时后

DESCRIPTION: (adapted from the application). Estrogen influence on synaptic connectivity in the aging hypothalamus of the female rat may be via modulation of neuromodulin (GAP-43) expression. Estrogen regulates reproductive activity throughout the lifetime of the female animal and is involved in neurite outgrowth during development, onset of the ovarian cycle, ovarian cycle regularity, and synaptic remodelling in the hypothalamus. Constant and high dosages of estradiol administered to female rats result in constant vaginal estrus, an age- related stage in reproductive senescence in which the ovaries are anovulatory, little steroidal hormones are secreted, and cyclicity ceases. It has been observed that increases and decreases in the concentration of specific proteins isolated from prepuberal female rats administered estrogen. One of the isolated proteins that showed a significant increase in expression levels, biochemically resembled neuromodulin, GAP-43 (kDa=4.3; pI=5.4). Neuromodulin is found in the developing rat nervous system, in neurite outgrowth of regenerating neurons and has also been shown to be involved in neuronal plasticity in the hippocampus. Recent studies have indicated that GAP-43 expression increases in the steroid primed animal. To date, the mechanism by which estrogen influences synaptic connectivity is unknown. It is our belief that estrogen facilitates this occurrence via modulation of neuromodulin, since neuromodulin is highly expressed in axons during neurite outgrowth in development and regeneration. We propose to determine whether aging or estrogen modulates changes in synaptic connectivity and GAP-43 expression in the aging hypothalamus. We aim to identify any changes in synaptic connectivity in the hypothalamus of the aging female rat which may be representative of changes in the ovarian cycle and vaginal epithelium and that those changes correlate with estrogen modulation of GAP-43 expression in neurons in the aging hypothalamus. Studies will be conducted in sexually mature adult (3 - 5 months) and older (8 - 10 months) female ovariectomized Sprague Dawley rats pretreated with estrogen or vehicle for 48 hours.