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.

Potential of lithium to reduce aluminium-induced cytotoxic effects in rat brain

“…Jyoti et al (2007) have also observed similar changes at the cellular level after Al treatment. Changes in the structure of synapse was also seen after Al treatment, which may affect neurotransmission and hence learning and memory processes in rats and the same is also observed in a number of studies (Rifat et al 1990;Hänninen et al 1994;Amador et al 2001). Al has been shown to alter the cholesterol, phospholipids, total lipids contents of the membranes and thus may be responsible for the membrane damage as seen in an earlier study from our lab ).…”

Aluminum-induced oxidative stress in lymphocytes of common carp (Cyprinus carpio)

“…Various studies have shown that this metal is able to displace Fe in different biomolecules and increase intracellular concentrations of the latter metal thereby promoting the Fenton reaction (Amador et al 2001;Yousef 2004). On the other hand, Al may damage the mitochondrion directly, affecting electron transport in the respiratory chain (Stohs and Bagchi 1995;Bondy and Cambell 2001).…”

Does neurotransmission impairment accompany aluminium neurotoxicity?

“…In the presence of aluminium, the uptake of neurotransmitters was found to be below control levels, with some exceptions [152,[227][228][229][230][231]. It is interesting to note that aluminium-induced stimulatory effects were only observed when uptake of neurotransmitters was analysed in brain slices [229] or in synaptic plasma membrane vesicles [152].…”