EXOGENOUS CHOLINE EFFECTS ON ACH FUNCTION IN BRAIN

迄今为止的实验证据表明，虽然补充 胆碱不改变乙酰胆碱的稳态浓度 (ACh)在正常的生化和生理条件下， 在药物诱导的神经元内ACh合成增加时， 需求 虽然利用这些技术所涉及的具体机制 补充胆碱合成乙酰胆碱期间增加的状态 神经元活动尚未阐明，结果表明，这 效果不是由于大脑中游离胆碱水平的增加，而是， 可能涉及的浓度或代谢的改变 含胆碱化合物。 因此，这是总体目标， 研究建议，以调查神经化学机制介导的 补充胆碱的效果。 神经化学和神经药理学 技术将被用来解决以下问题：1）做慢性 胆碱可利用性的改变改变ACh的动力学 新陈代谢？ 2)是利用补充胆碱， 乙酰胆碱的合成依赖于胆碱能活性水平 神经元？ 3)胆碱的来源是什么？ 胆碱补充剂？ 4)有哪些机制来管理 胆碱在神经末梢的代谢 5)什么是自然和 血清因子的生理意义， 浓度是由胆碱补充诱导的，其作用可能是 来调节胆碱穿过血脑屏障的运输 六、 补充胆碱的功能后果是什么？ （第7段） 补充胆碱对成年人大脑的影响 老鼠在老年动物的大脑中表现出什么？ 这些研究的结果将 提供了神经递质前体 可用性和中枢胆碱能机制，这是必不可少的 了解调节胆碱代谢的内在机制 和脑内乙酰胆碱。 此外，这些结果可以为更好地 评估使用胆碱的治疗原理和可能的优点 用于治疗神经精神疾病， 低胆碱能活性，如阿尔茨海默病。

Experimental evidence to date indicate that although supplementation with choline does not alter the steady-state concentration of acetylcholine (ACh) in brain under normal biochemical and physiological conditions, it does support the synthesis of ACh during drug-induced increases in neuronal demand. Although the specific mechanisms involved in the utilization of supplemental choline for the synthesis of ACh during states of increased neuronal activity have not yet been elucidated, results indicate that this effect is not due to increased levels of free choline in brain, but rather, may involve alterations in the concentration or metabolism of choline-containing compounds. Hence, it is the overall objective of this research proposal to investigate the neurochemical mechanisms mediating the effects of choline supplementation. Neurochemical and neuropharmacological techniques will be used to address the following questions: 1) Do chronic alterations in the availability of choline alter the dynamics of ACh metabolism? 2) Is the utilization of supplemental choline for the synthesis of ACh dependent on the level of activity of cholinergic neurons? 3) What are the sources of choline mediating the effects of choline supplementation? 4) What are the mechanisms regulating the metabolism of choline at nerve terminals? 5) What is the nature and physiological significance of the serum factor whose activity or concentration is induced by choline supplementation and whose role may be to regulate the transport of choline across the blood-brain barrier? 6) What are the functional consequences of choline supplementation? and 7) Are the effects of choline supplementation observed in brain from adult rats manifest in brain from aged animals? Results from these studies will provide information on the relationship between neurotransmitter precursor availability and central cholinergic mechanisms which is essential for understanding the intrinsic mechanisms regulating the metabolism of choline and ACh in brain. Furthermore, results may provide a basis to better assess the therapeutic rationale and possible merits of the use of choline for the treatment of neuropsychiatric disorders postulated to involve hypocholinergic activity such as Alzheimer's Disease.