title: Lipid peroxidation and aluminium effects on the cholinergic system in nerve terminals.
abstract: In the present study, we analyzed how aluminium and oxidative stress induced by ascorbate/Fe(2+) affect the mechanisms related with the cholinergic system in a crude synaptosomal fraction isolated from rat brain. [(3)H]Choline uptake, [(3)H]acetylcholine release, membrane potential and Na(+)/K(+)-ATPase activity were determined in the presence or in the absence of aluminium in control conditions and in the presence of ascorbate (0.8 mM)/Fe(2+) (2.5 micro M). The extent of lipid peroxidation was measured by quantifying thiobarbituric acid reactive substances (TBARS). Under oxidizing conditions aluminium increased the formation of TBARS by about 30%, but was without effect when the synaptosomal preparation was incubated in the absence of oxidants. Additionally, aluminium potentiated the inhibition of the high-affinity [(3)H]choline uptake observed following lipid peroxidation and had the same effect on the Na(+)/K(+)-ATPase activity. [(3)H]Acetylcholine release induced by 4-aminopyridine, and membrane potential were not significantly affected under oxidizing conditions, either in the absence or in the presence of aluminium. We can conclude that aluminium, by potentiating lipid peroxidation, affects the uptake of choline in nerve endings. This effect, occurring during brain oxidative injury, might contribute to the cholinergic dysfunction and neuronal cell degeneration known to occur in Alzheimer's disease.
authors.affiliation: Center for Neurosciences of Coimbra, Department of Zoology and Faculty of Medicine, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: F C
authors.initials: FC
authors.lastname: Amador
authors.forename: M S
authors.initials: MS
authors.lastname: Santos
authors.forename: C R
authors.initials: CR
authors.lastname: Oliveira