A pharmacological analysis of aluminum effects on the central nervous system

Abstract

The possible causes of dementia are many, and most cases are associated with degenerative disease of the central nervous system; therefore, analysis of neurotransmitter systems may provide valuable information on the selectivity of the degenerative process. This report will deal with an experimental approach to dementia, through quantitative analysis of electroencephalographic (EEG) effects induced by aluminum on laboratory animals. In a first series of experiments we found that single oral doses of aluminum hydroxide induced in mice a dose-dependent diminution of the EEG power of 7.5 to 12 c/s frequency band, and a parallel dose-dependent increase of aluminum content in the brain, as early as 45 minutes after administration. It indicated that aluminum hydroxide is readily absorbed through an empty stomach or duodenum and is able to induced alterations of background EEG rhythms at doses equivalent to the ones used in human therapy. These and other data suggest that the EEG disturbances of background type, which are observed during the early stage in dialysis encephalopathy in man, may be due at least in part to a pharmacological and therefore reversible effect induced by an increased aluminum level in the brain. This effect was therefore investigated in a second series of experiments. Aluminum was found to induce, even in minute doses, profound effects on the hippocampal EEG of the rabbit after acute intracerebro-ventricular administration, consisting of long-lasting EEG desynchronization and, at higher doses, of EEG epileptiform pattern. These effects could be at least in part reversed or prevented by i.v. administration of drugs effective on the cholinergic and/or endorphinic systems. These results, although preliminary in nature, may contribute to the elucidation of the pathogenesis of experimental ‘dementia’ models in animals.