EXOGENOUS CHOLINE EFFECTS ON ACH FUNCTION IN BRAIN

迄今为止的实验证据表明，尽管补充了 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，它 在药物诱导的神经元增加过程中确实支持ACh的合成 需求。尽管涉及到利用的具体机制 补充胆碱对乙酰胆碱合成的影响 神经元的活动尚未被阐明，结果表明这 这种影响并不是由于大脑中游离胆碱水平的增加，而是因为， 可能涉及浓度或新陈代谢的改变 含有胆碱的化合物。因此，这是一个总的目标。 关于研究神经化学机制的建议 补充胆碱的效果。神经化学和神经药理学 将使用技术来解决以下问题：1)做慢性 胆碱可利用性的改变改变了ACh的动力学 新陈代谢？2)补充胆碱对健康的利用 胆碱能活性水平对乙酰胆碱合成的影响 神经元？3)胆碱的来源是什么？ 胆碱补充？4)是什么机制调节 胆碱在神经末梢的代谢？5)胆碱的性质和 血清因子活性或功能的生理学意义 浓度是由补充胆碱引起的，其作用可能是 来调节胆碱通过血脑屏障的运输？6) 补充胆碱的功能后果是什么？和7) 补充胆碱对成人大脑有影响吗？ 老年动物的大脑中出现了老鼠吗？这些研究的结果将 提供有关神经递质前体之间关系的信息 可获得性和中枢胆碱能机制 了解胆碱代谢的内在调节机制 大脑也会酸痛。此外，研究结果可能会为更好地 评估使用胆碱的治疗原理和可能的优点 用于治疗神经精神障碍，假设涉及 低胆碱能活动，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.