0000000000395266
AUTHOR
Andrea Köppen
Free choline and choline metabolites in rat brain and body fluids: sensitive determination and implications for choline supply to the brain.
In the central nervous system, choline is an essential precursor of choline-containing phospholipids in neurons and glial cells and of acetylcholine in cholinergic neurons. In order to study choline transport and metabolism in the brain, we developed a comprehensive methodical procedure for the analysis of choline and its major metabolites which involves a separation step, selective hydrolysis and subsequent determination of free choline by HPLC and electrochemical detection. In the present paper, we report the levels of choline, acetylcholine, phosphocholine, glycerophosphocholine and choline-containing phospholipids in brain tissue, cerebrospinal fluid and blood plasma of the untreated ra…
The Homeostasis of Brain Choline
The interest in the homeostasis of brain choline is reinforced by the role of choline as immediate precursor of acetylcholine, phosphatidylcholine and other phospholipids in the brain. In order to obtain a comprehensive view of the mochanisms of homeostasis it appeared necessary to elucidate the negative arteriovenous difference of choline across the brain (net release), a phenomenon that has been known for 20 years and is present in mammals and in man. This finding prompted an intense search for a de novo synthesis of choline in the brain. We detected in anaesthetized rats a reversal of the net release into a net uptake (positive arterio-venous difference), when the plasma level of choline…
Modulation of hippocampal acetylcholine release after fimbria-fornix lesions and septal transplantation in rats
Abstract Female Long–Evans rats sustained electrolytic lesions of the fimbria and the dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks later, the rats received intra-hippocampal grafts of fetal septal cell suspensions. Nine to twelve months later, the release of acetylcholine (ACh) in the hippocampus of sham-operated, lesion-only and grafted rats was measured by microdialysis. The extent of cholinergic (re)innervation was determined by acetylcholinesterase (AChE) staining and densitometry. In both lesion-only and grafted rats, the ratio of ACh release to AChE staining intensity was increased as compared to sham-operated rats, indicating a loss of endogenous …
Uptake and storage of choline by rat brain: influence of dietary choline supplementation.
In order to elucidate the regulation of the levels of free choline in the brain, we investigated the influence of chronic and acute choline administration on choline levels in blood, CSF, and brain of the rat and on net movements of choline into and out of the brain as calculated from the arteriovenous differences of choline across the brain. Dietary choline supplementation led to an increase in plasma choline levels of 50% and to an increase in the net release of choline from the brain as compared to a matched group of animals which were kept on a standard diet and exhibited identical arterial plasma levels. Moreover, the choline concentration in the CSF and brain tissue was doubled. In th…
Regulation of free choline in rat brain: dietary and pharmacological manipulations.
The present study analyses, comparatively, the kinetics of free choline in the brain of rats during dietary and pharmacological manipulations. Low-choline diet halved the choline plasma level but did not cause significant changes of CSF choline. High-choline diet, hypoxia and treatment with nicotinamide increased brain choline availability through a central site of action and increased the CSF choline concentration. CSF choline concentrations were more effectively elevated by nicotinamide treatment (20-25 microM) than by acute choline administration (13-15 microM). Increases of CSF choline, due to brain choline mobilization, were consistently associated with a net release of choline from th…
Uptake and metabolism of choline by rat brain after acute choline administration.
The present study is concerned with the uptake and metabolism of choline by the rat brain. Intraperitoneal administration of choline chloride (4-60 mg/kg) caused a dose-dependent elevation of the plasma choline concentration from 11.8 to up to 165.2 microM within 10 min and the reversal of the negative arteriovenous difference (AVD) of choline across the brain to positive values at plasma choline levels of greater than 23 microM. Net choline release and uptake were linearly dependent on the plasma choline level in the physiological range of 10-50 microM, whereas the CSF choline level was significantly increased only at plasma choline levels of greater than 50 microM. The bolus injection of …
Effects of nicotinamide on central cholinergic transmission and on spatial learning in rats
High-dose nicotinamide (1000 mg/kg) leads to a minor increase of plasma choline but to a major increase of the choline concentrations in the intra- and extracellular spaces of the brain. In the hippocampus, the nicotinamide-induced increase in choline was associated with an increase in the release of acetylcholine under stimulated conditions. In young rats, nicotinamide in doses between 10 and 1000 mg/kg did not influence spatial learning, as tested in the Morris water maze. In old rats, low doses of nicotinamide were ineffective whereas the high dose of 1000 mg/kg even impaired spatial learning. The combined administration of choline and nicotinamide had a synergistic effect on brain choli…
Release of choline from rat brain under hypoxia: contribution from phospholipase A2 but not from phospholipase D
Moderate hypoxia induced in rats by inhalation of 10% oxygen led to an increase of the concentration of free choline in the brain and caused a large net-release of choline from the brain into the venous blood as determined by the measurement of the arterio-venous difference. In hippocampal slices from rat brain, hypoxia increased the release of choline into the superfusion medium. The activity of phospholipase D, as measured by the formation of phosphatidylpropanol in the presence of propanol, was not stimulated under these conditions. However, the mobilization of choline was completely depressed by lowering extracellular calcium and by 0.1 mM mepacrine. We conclude that hypoxia leads to a …
Chapter 23: Choline, a precursor of acetylcholine and phospholipids in the brain
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 exha…
Small rises in plasma choline reverse the negative arteriovenous difference of brain choline.
The concentrations of free choline in blood plasma from a peripheral artery and from the transverse sinus, in the CSF, and in total brain homogenate, have been measured in untreated rats and in rats after acute intraperitoneal administration of choline chloride. In untreated rats, the arteriovenous difference of brain choline was related to the arterial choline level. At low arterial blood levels (less than 10 microM) as observed under fasting conditions, the arteriovenous difference was negative (about -2 microM), indicating a net release of choline from the brain of about 1.6 nmol/g/min. In rats with spontaneously high arterial blood levels (greater than 15 microM), the arteriovenous diff…