Aluminium impairs glucose utilization and cholinergic activity in rat brain in vitro

The effects of AlCl3 on the producton of 14C02 from (U-14C) glucose and high affinity choline transport in rat brain synaptosomes, and on carbachol-stimulated hydrolysis of phosphoinositides in cortical slices were studied. In buffer containing either high K+ (50 mM) or low K+ (4.9mM), 1 mM, AlCl3 depressed the evolution of 14CO2 from (U-14C)-glucose to 54% and 44% of control rates, respectively. At a concentration of 0.1 mM, AlCl3 depressed the evolution of 14CO2 from (U-14C)-glucose from synaptosomes incubated in the high K+ buffer, but did not significantly change 14CO2 production from synaptosomes in the low K+ buffer. Aluminium chloride also inhibited high affinity choline transport in synaptosomes prepared from rat cortex and from hippocampus with an IC50 of approximately 0.5 mM. In brain slices the carvacholstimulated hydrolysis of phosphoinositides was inhibited by AlCl3 in a dose-dependent manner. One millimolar, 0.5 mM and 0.1 mM AlCl3 inhibited the carbachol-stimulated release of inositol phosphates by 75%, 44% and 33%, respectively. These same concentrations of AlCl3 inhibited the incorporation of (3H) inositol into phospholipids. This inhibitory effect was not dose-dependent as all 3 concentrations of AlCl3 inhibited phospholipid labelling to the same extent (27-37%). These results are discussed in relation to the in vivo neurotoxicity of aluminium. (author)