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

Abstract

The effects of AlCl 3 on the production of 14CO 2 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 + (4.9 mM), 1 mM AlCl 3 significantly depressed the synaptosomal production of 14CO 2 from [U- 14C]-glucose to 54% and 44% of control rates, respectively. At a concentration of 0.1 mM, AlCl 3 depressed the evolution of 14CO 2 from [U- 14C]glucose from synaptosomes incubated in the high K + buffer, but did not significantly change 14CO 2 production from synaptosomes in the low K + buffer. Aluminum chloride also inhibited high affinity choline transport in synaptosomes prepared from rat cortex and from hippocampus with an IC 50 of approximately 0.5 mM. In brain slices the carbachol-stimulated hydrolysis of phosphoinositides was inhibited by AlCl 3 in a dose-dependent manner. One millimolar, 0.5 mM and 0.1 mM AlCl 3 inhibited the carbachol-stimulated release of inositol phosphates by 75%, 44% and 33%, respectively. These same concentrations of AlCl 3 inhibited the incorporation of [ 3H] inositol into phospholipids. This inhibitory effect was not dose-dependent as all 3 concentrations of AlCl 3 inhibited phospholipid labelling to the same extent (27–37%). These results are discussed in relation to the in vivo neurotoxicity of aluminum.