TIME FRAMES OF CHOLINE ENHANCEMENT OF MEMORY

胆碱增强记忆的时间范围

• 批准号: 6267502
• 负责人: CHRISTINA L WILLIAMS
• 金额: $ 19.74万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-15 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6267502
• 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 在出生前和出生后发育期间给予大鼠的补充剂 产生长期的生物化学和神经解剖学的改变， 基底前脑胆碱能功能的标志物和长期 促进视觉空间记忆作为索引的选择准确性， 辐射臂迷宫，并似乎防止年龄相关的下降， 记忆功能 雄性大鼠补充胆碱会产生这些 记忆功能的组织变化只有在 胚胎期（艾德）12-17天或出生后（PD）16-30天，但在 PD 1-15，当几个潜在的重要发育事件 发生在老鼠身上。 该提案的主要目标是1）。到 评估这些多个敏感时期的可能解释， 胆碱有效性和2.）来研究行为的个体发育 胆碱补充/缺乏的影响。 将评估三个假设：1）。性别差异 假设预测在PD期间暴露于性腺类固醇激素 15-30是胆碱对PD 15-30发挥作用所必需的。 初步数据显示，新生儿阉割 降低了围产期胆碱补充剂对 视觉空间记忆 计划进行研究以确定活性激素 （睾酮或其代谢物雌二醇）用于增强 补充胆碱的效果。2)胆碱饱和假说 表明幼犬可能接受了异常高水平的胆碱 在PD 1-15期间从乳汁中排出，因此幼仔的系统可能已经饱和 补充胆碱并没有增加效果。 这 假设将通过与已知的 牛奶中的胆碱含量较低。3.）第三章甜菜碱作为活性剂 假设表明胆碱可能发挥其行为效应 甜菜碱是一种化合物， 甲硫氨酸和叶酸代谢重要甲基供体。 以来 胆碱向甜菜碱的转化可以在子宫内发生， 出生后慢慢地，在第一个阶段，几乎没有甜菜碱是由胆碱制成的。 产后一周 为了验证这一假设，将用以下物质处理大鼠： 甜菜碱在大鼠近端使用能力发展的各个时期 和远端线索导航也将检查甜菜碱，和 补充胆碱和缺乏胆碱的大鼠。 这些数据应 为我们提供了关于发育，激素调节， 和天然营养控制胆碱的组织促进作用 视觉空间记忆