PRENATAL CHOLINE AVAILABILITY: IMPACT ON AGE-RELATED DEFICITS IN SLEEP AND MEMORY

产前胆碱可用性：对年龄相关的睡眠和记忆力缺陷的影响

• 批准号: 7309744
• 负责人: WARREN H MECK
• 金额: $ 14.54万
• 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/7309744
• 关键词: REM sleep; age difference; aging; animal old age; apolipoprotein E; auditory stimulus; behavior test; behavioral /social science research tag; biological models; choline; choline deficiency; conditioning; developmental neurobiology; dietary supplements; folate deficiency; gene dosage; juvenile animal; laboratory mouse; laboratory rat; mature animal; memory; memory disorders; mother /embryo /fetus nutrition; neural information processing; nutrient bioavailability; nutrition related tag; perinatal; sleep disorders

Separate lines of evidence have shown that age-related impairments in memory are correlated with the prenatal availability of choline and changes in rapid eye movement (REM) sleep. For example, prenatal choline supplementation leads to adult modifications in cholinergic metabolism that are associated with enhancements in cognition and reduced age-related decline in memory. In addition, evidence that deficits in both REM sleep and memory are ameliorated in adult animals by cholinergic agonists suggests that organizational changes in cholinergic metabolism may be able to alter the structure and continuity of sleep in adulthood and directly influence cognitive processes. In order to investigate the relationship between sleep and the prenatal availability of choline, baseline levels of REM and slow-wave sleep (SWS) will be measured as a function of prenatal choline deficiency, sufficiency, and supplementation in adult rats. The overall goals of the project are to conduct a series of studies that will determine if adult animals with variations in choline metabolism caused by the prenatal availability of choline have selective alterations in the quantity or quality of sleep that are evident early in adulthood and are sustained or enhanced with aging. The proposed studies will also examine whether changes in sleep patterns (e.g., ratio of SWS to REM sleep) are associated with age-related changes in behavior and whether different types of behavioral tasks (e.g., hippocampal or non-hippocampal dependent) are differentially sensitive to alterations in sleep patterns as a function of age and early choline availability. Ensemble recording techniques will be used in order to access the efficacy of hippocampal-neocortical reactivation mechanisms that may be involved in the consolidation of memory processes as a function of the prenatal availability of choline in 4 mo, 14 mo, and 24+ mo old rats. A final series of experiments is designed to develop a murine model of cholinergic metabolism as a function of apolipoprotein e-deficiency, prenatal choline availability, gene dosage, and age. All of these studies are designed to evaluate the relationships between sleep control mechanisms and the memory enhancing effects of prenatal choline supplementation in young, mature, and aged animals.

不同的证据表明，与年龄相关的记忆障碍与产前胆碱的可用性和快速眼动（REM）睡眠的变化有关。例如，产前补充胆碱会导致成年后胆碱能代谢的改变，这与认知能力的增强和与年龄相关的记忆力下降的减少有关。此外，有证据表明胆碱能激动剂可以改善成年动物的快速眼动睡眠和记忆缺陷，这表明胆碱能代谢的组织变化可能能够改变成年期睡眠的结构和连续性，并直接影响认知过程。为了研究睡眠与产前胆碱可用性之间的关系，将测量成年大鼠的 REM 和慢波睡眠 (SWS) 基线水平，作为产前胆碱缺乏、充足和补充的函数。总体目标 该项目的目的是进行一系列研究，以确定因产前胆碱供应而导致胆碱代谢变化的成年动物是否会选择性地改变睡眠质量或睡眠质量，这种改变在成年早期就很明显，并且通过以下措施可以持续或增强：老化。拟议的研究还将检查睡眠模式的变化（例如，SWS 与 REM 睡眠的比率）是否与年龄相关的行为变化相关，以及不同类型的行为任务（例如，海马或非海马）是否与年龄有关。 依赖）对睡眠模式的变化作为年龄和功能的函数有不同的敏感度 早期胆碱的可用性。将使用整体记录技术来评估海马-新皮质再激活机制的功效，该机制可能参与记忆过程的巩固，作为 4 个月、14 个月和 24 个月以上大鼠的产前胆碱可用性的函数。最后一系列实验旨在开发胆碱能代谢的小鼠模型，该模型与载脂蛋白 e 缺乏、产前胆碱可用性、基因剂量和年龄有关。所有这些研究都旨在评估年轻、成熟和老年动物的睡眠控制机制与产前补充胆碱的记忆增强效果之间的关系。