CAN THE MECHANISMS OF ALUMINUM NEUROTOXICITY BE INTEGRATED INTO A UNIFIED SCHEME

Regardless of the host, the route of administration, or the speciation , aluminum is a potent neurotoxicant. In the young adult or developmen tally mature host, the neuronal response to Al exposure can be dichoto mized on morphological grounds. In one, intraneuronal neurofilamentous aggregates are formed whereas in the other, significant neurochemical and neurophysiological perturbations are induced without neurofilamen tous aggregate formation. Evidence is presented that the induction of neurofilamentous aggregates is a consequence of alterations in the pos ttranslational processing of neurofilament (NF), particularly with reg ard to phosphorylation state. Although Al has been reported to impact on gene expression, this does not appear to be critical to the inducti on of cytoskeletal pathology. In hosts responding to Al exposure witho ut the induction of cytoskeletal pathology, impairments in glucose uti lization, agonist-stimulated inositol phosphate accumulation, free rad ical-mediated cytotoxicity, lipid peroxidation, reduced cholinergic fu nction, and altered protein phosphorylation have been described. The e xtent to which these neurochemical modifications correlate with the in duction of a characteristic neurobehavioral state is unknown. In addit ion to these paradigms, Al is toxic in the immediate postnatal interva l.