REGULATION OF FREE CHOLINE IN RAT-BRAIN - DIETARY AND PHARMACOLOGICALMANIPULATIONS

The present study analyses, comparatively, the kinetics of free cholin e in the brain of rats during dietary and pharmacological manipulation s. Low-choline diet halved the choline plasma level but did not cause significant changes of CSF choline. High-choline diet, hypoxia and tre atment 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 nicotinam ide treatment (20-25 mu M) than by acute choline administration (13-15 mu M). Increases of CSF choline, due to brain choline mobilization, w ere consistently associated with a net release of choline from the bra in as reflected by strongly negative arterio-venous differences (AVD) of brain choline. The balance between release and uptake of brain chol ine was controlled by the arterial plasma choline level in all treatme nt groups; however, the normal 'reversal point' of 15 mu M - represent ing the plasma choline level where uptake and release of brain choline are balanced - was shifted to more than 40 mu M by high-choline diet and nicotinamide. In conclusion, our data characterize the release of choline into the venous blood as an important component of brain choli ne homeostasis. Furthermore, we demonstrate that the concentration of brain choline (e.g. as a precursor of acetylcholine) can be enhanced m ore efficiently by manipulating choline homeostatic mechanisms than by acute choline administration. (C) 1998 Elsevier Science Ltd. All righ ts reserved.