TIME FRAMES OF CHOLINE ENHANCEMENT OF MEMORY

胆碱增强记忆的时间范围

• 批准号: 3746089
• 负责人: CHRISTINA L WILLIAMS
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746089
• 关键词: age difference; behavior test; betaine compound; choline; developmental neurobiology; developmental nutrition; dietary supplements; estradiol; female; folate; gender difference; hormone regulation /control mechanism; laboratory rat; male; male castration; memory; milk; molecular psychobiology; neurotrophic factors; nutrition related tag; perinatal; sex hormones; space perception; testosterone; vitamin metabolism

Recent work from our laboratory has demonstrated that choline supplementation given to rats during both pre- and postnatal development produces long-term modification of biochemical and neuroanatomical markers of basal forebrain cholinergic function and long-term facilitation of visuospatial memory as indexed by choice accuracy on a radial-arm maze, and appears to protect against age-related decline in memory function. Choline supplementation to male rats produces these organizational changes in memory function only when given during embryonic days (ED) 12-17 or postnatal days (PD) 16-30, but not during PD 1-15 when several potentially important developmental events are occurring in the rat. The major goal of this proposal are 1.) to evaluate possible explanations of these multiple sensitive periods of choline effectiveness and 2.) to examine the ontogeny of the behavioral effects of choline supplementation/deficiency. Three hypotheses will be evaluated: 1.) The Sexual Differentiation Hypothesis predicts that exposure to gonadal steroid hormones during PD 15-30 is required for choline to exert its effects on PD 15-30. Preliminary data has shown that neonatal castration significantly decreases the effectiveness of perinatal choline supplementation on visuospatial memory. Studies are planned to determine the active hormone (testosterone or its metabolite estradiol) for the enhancement of the effect of choline supplementation. 2) The Choline Saturation Hypothesis suggests that pups may be receiving exceptionally high levels of choline from milk during PD 1-15, thus the pups' system may already be saturated with choline and supplementation would have no added effect. This hypothesis will be tested by raising pups with dams that are known to have lower milk choline levels. 3.) The Betaine as Active Agent Hypothesis suggests that choline may be exerting its behavioral effects on memory through its conversion to betaine, a compound that is an important methyl donor for methionine and folate metabolism. Since the conversion of choline to betaine can occur in utero and only develops slowly after birth, little betaine is made from choline during the first postnatal week. To test this hypothesis rats will be treated with betaine at various periods of development of rats ability to use proximal and distal cues to navigate will also be examined in betaine-,and choline-supplemented and choline-deficient rats. These data should provide us with information about the development, hormonal modulation, and natural nutritional control of choline's organizational facilitation of visuospatial memory.

我们实验室最近的研究表明，胆碱 在大鼠出生前和出生后发育期间给予补充剂 产生生化和神经解剖学的长期修饰 基底前脑胆碱能功能的标志物与远期 通过选择准确率对视觉空间记忆进行索引的便利性 放射臂迷宫，似乎可以防止年龄相关性的下降 记忆功能。对雄性大鼠补充胆碱会产生这些 记忆功能的组织变化仅在过程中给出 胚胎天数(ED)12-17或出生后天数(PD)16-30，但不在 PD 1-15当几个潜在的重要发育事件 在老鼠体内发生的。这项提议的主要目标是1。)至 评估对这多个敏感期的可能解释 胆碱疗效和2。)来考察行为的个体发生学 胆碱补充/缺乏的影响。 将评估三个假设：1)性别分化 假说预测帕金森病期间暴露于性腺类固醇激素 胆碱对PD 15-30起作用需要15-30个胆碱。 初步数据显示，新生儿阉割显著 降低围产期补充胆碱的有效性 视觉空间记忆。计划进行研究以确定活性荷尔蒙 (睾酮或其代谢物雌二醇) 补充胆碱的效果。2)胆碱饱和假说 这表明幼崽可能接受了异常高水平的胆碱 在PD 1-15期间来自牛奶，因此幼崽的系统可能已经饱和 服用胆碱和补充剂不会有额外的效果。这 假设将通过用已知的水坝饲养幼崽来检验 牛奶胆碱水平较低。3.)甜菜碱作为活性物质 假说表明胆碱可能正在发挥其行为作用 通过它转化为甜菜碱的记忆，甜菜碱是一种化合物 蛋氨酸和叶酸代谢的重要甲基供体。自.以来 胆碱转化为甜菜碱可以在子宫中发生，只有在发育过程中才会发生。 慢慢地，在出生后的第一个阶段，很少的甜菜碱是由胆碱制成的。 出生后一周。为了验证这一假说，老鼠将被用 甜菜碱在不同发育时期大鼠近端利用能力的研究 而导航的远端提示也将在甜菜碱中进行检查--和 胆碱补充和胆碱缺乏大鼠。这些数据应该 为我们提供有关发育，荷尔蒙调节， 和自然营养调控胆碱的组织易化 视觉空间记忆。