TIME FRAMES OF CHOLINE ENHANCEMENT OF MEMORY

胆碱增强记忆的时间范围

• 批准号: 3768424
• 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/3768424
• 关键词: behavior test; choline; developmental neurobiology; developmental nutrition; dietary supplements; estradiol; gender difference; gestational age; hormone regulation /control mechanism; infant animal; laboratory rat; memory; milk; molecular psychobiology; newborn animals; nutrition related tag; perinatal; sex hormones

Recent work from our laboratories have demonstrated the 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 maze. Choline supplementation to male rats produces these organizational changes in visuospatial memory only when given during embryonic days 12-17 or postnatal days 16-30 but not during postnatal days 1-15 when several potentially important developmental events are occurring in the rat. The major goal of this proposal is to further evaluate these multiple sensitive periods of choline effectiveness. Two hypotheses will be tested. 1. The sexual differentiation hypothesis predicts that exposure to gonadal steroid hormones during postnatal days 1-15 is required for choline to exert its effects on postnatal days 15-30. Preliminary data demonstrating that female rats are only sensitive to choline action when it is administered prenatally support this hypothesis. Two lines of research are planned to examine this phenomenon. Gonadal hormone exposure during early postnatal development will be manipulated and subjects will be tested as adults for their visuospatial memory using a radial arm maze task with both working and reference memory comment of spatial memory using a water maze navigational task. 2. The choline saturation hypothesis suggests that pups may be receiving exceptionally high levels of choline from the dams milk during postnatal day 1-15, thus supplemental choline may not be able to enhance brain choline exposure during this period. This hypothesis will be tested by raising pups with mothers of different lactational states in order to vary their exposure to choline naturally occurring in the dam's milk. For all these studies, subjects will be exposed to choline during one of 4 periods of development (Prenatal days 12-17, postnatal days 1-15, 16-30, or prenatal day 12-postnatal day 30) or not exposed to choline. These data should provide us with information about the development, hormonal modulation, and natural nutritional control of choline's organizational facilitation of visuospatial memory.

我们实验室最近的工作证明了胆碱 在出生前和出生后发育期间给予大鼠的补充剂 产生生化和神经解剖学标记的长期改变 基底前脑胆碱能功能和长期促进 视觉空间记忆，以径向迷宫中的选择准确度为指标。 雄性大鼠补充胆碱会产生这些组织变化 只有在胚胎期12-17天给予时， 出生后第16-30天，但出生后第1-15天， 在大鼠中发生了潜在的重要发育事件。 的 这项建议的主要目标是进一步评估这些多个敏感的 胆碱有效期。 将检验两个假设。 1.的 性分化假说预测，接触性腺类固醇 激素在出生后1-15天，胆碱需要发挥其 对产后15-30天的影响。 初步数据表明， 雌性大鼠仅在服用胆碱时对胆碱的作用敏感 产前支持这一假设。 计划进行两项研究， 研究这一现象。 出生后早期的性激素暴露 发展将被操纵，受试者将作为成年人进行测试， 他们的视觉空间记忆使用径向臂迷宫任务， 利用水迷宫对空间记忆的参考记忆评价 导航任务 2.胆碱饱和假说表明 可能从母奶中获得了异常高水平的胆碱 在出生后第1-15天，因此补充胆碱可能无法 在此期间增加脑胆碱暴露。 这一假设将是 通过与不同哺乳期的母亲一起抚养幼崽进行测试， 为了改变它们对天然存在于母体中的胆碱的接触， 牛奶 对于所有这些研究，受试者将暴露于胆碱， 4个发育期之一（产前12-17天，产后1-15天， 16-30天，或出生前第12天-出生后第30天）或不暴露于胆碱。 这些数据应该可以为我们提供有关发展的信息， 激素调节和胆碱的天然营养控制 视觉空间记忆的组织促进。