Mj. Strong et al., CAN THE MECHANISMS OF ALUMINUM NEUROTOXICITY BE INTEGRATED INTO A UNIFIED SCHEME, Journal of toxicology and environmental health, 48(6), 1996, pp. 599-613
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.