Department of Physiology, Hallym University, College of Medicine, Chunchon, 24252, Korea.
Curr Neuropharmacol. 2018;16(1):51-58. doi: 10.2174/1570159X15666170518150053.
Choline alfoscerate (α-GPC) and Cytidine 5'-diphosphocholine (CDPCholine) are both acetylcholine precursors and are considered to act as pro-cholinergic nootropic agents. Acetylcholine precursors have also recently found frequent use in the neurology clinic. Stroke and many types of dementia have been shown to respond favorably after treatment with these agents, not only in terms of cognitive dysfunction but also behavioral and psychological symptoms. The primary mechanisms of Acetylcholine precursors are the following: 1) Acetylcholine precursors themselves are used in the biosynthesis of acetylcholine and 2) byproducts like glycerophosphate have protective functions for neuronal phospholipids. However, whether acetylcholine precursors have a similar effect in treating cognitive impairment in patients with epilepsy remains controversial.
Our previous studies investigating acetylcholine precursors in seizure-experienced animals have produced variable results that were dependent on the timing of administration.
Early administration of CDP-choline immediately after seizure increased neuronal death, blood-brain barrier (BBB) disruption and microglial activation in the hippocampus. However, administration of α-GPC starting 3 weeks after seizure (late administration) improved cognitive function through reduced neuronal death and BBB disruption, and increased neurogenesis in the hippocampus.
These seemingly contradictory results may be attributed to both epileptogenic features and neuroprotective functions of several acetylcholine precursors.
胆碱酒石酸氢盐（α-GPC）和胞苷 5′-二磷酸胆碱（CDPCholine）都是乙酰胆碱的前体，被认为是拟胆碱能促智药。乙酰胆碱前体最近也在神经病学临床中频繁使用。这些药物不仅在认知功能障碍方面，而且在行为和心理症状方面，对中风和许多类型的痴呆症的治疗都有良好的反应。乙酰胆碱前体的主要机制如下：1）乙酰胆碱前体本身用于乙酰胆碱的生物合成，2）甘油磷酸等副产物对神经元磷脂具有保护作用。然而，乙酰胆碱前体在治疗癫痫患者的认知障碍方面是否具有类似的作用仍存在争议。
我们之前对经历过癫痫发作的动物进行的乙酰胆碱前体研究产生了不同的结果，这些结果取决于给药时间。
癫痫发作后立即给予 CDP-胆碱（早期给药）会增加海马中的神经元死亡、血脑屏障（BBB）破坏和小胶质细胞激活。然而，从癫痫发作后 3 周开始给予 α-GPC（晚期给药）会通过减少神经元死亡和 BBB 破坏以及增加海马中的神经发生来改善认知功能。
这些看似矛盾的结果可能归因于几种乙酰胆碱前体的致痫特征和神经保护功能。
