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RESEARCH PRODUCT

Chapter 23: Choline, a precursor of acetylcholine and phospholipids in the brain

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Publisher Summary The plasma level of free choline is remarkably constant at about 10 pM in animals and human. Ingestion of food, especially when rich in choline or lecithin, transiently elevates the plasma choline level up to 20 pM or more. In contrast, choline-deficient diet leads to a reduction of the plasma level by about 50%. Choline is considered an essential nutrient, which is predominantly supplied as phosphatidylcholine (lecithin). For a long time, neuroscientists have been intrigued by the fact that choline is a precursor for the biosynthesis of both acetylcholine (ACh) and phospholipids. For 50 years, lecithin has been marketed in Europe as a drug that was claimed to prevent exhaustion of membrane phospholipids in the CNS and therefore could reinforce “neuronal strength”. More recently, Wurtman and his colleagues suggested that partial degeneration of a cholinergic pathway may lead to an over-activity of the remaining viable neurones and consequently to exhaustion of the ACh pools of these neurons. The enhanced ACh turnover may in turn attack those synaptic phospholipid stores that serve as a source of choline for transmitter synthesis. Administration of choline or lecithin might then ameliorate the symptoms of chronic diseases that are caused by cholinergic hypofunction. These speculations stimulated a number of research activities in the cholinergic field. Unequivocal experimental evidence for the validity of the hypotheses in animals and especially in man is still lacking. Among the theoretical arguments against the above hypotheses was the general belief that the “milieu interne” of the brain, which is maintained by the blood-brain-barrier (BBB) and other mechanisms, protects the brain from fluctuations in the plasma levels of essential nutrients. In the case of choline, however, the BBB does not buffer fluctuations in the plasma level, because the carrier-mediated transport through the BBB is highly unsaturated at physiological plasma levels of choline. Therefore, homeostatic mechanisms of brain choline, if they exist, should be localized beyond the BBB within the CNS. This chapter discusses the existence and the nature of these homeostatic mechanisms and the results are summarized.