Age‐Related Differences in Synaptosomal Peroxidative Damage and Membrane Properties

Abstract

Young, adult, and old rats were used to study the effect of age on the integrity and functioning of brain synaptosomes. An evaluation was made of the differences in lipid composition, membrane fluidity, Na+, K(+)-ATPase activity, and susceptibility to in vitro lipid peroxidation. There was an age-related increase in synaptosomal free fatty acids, with no modification in acyl chain composition, and a decrease in membrane phospholipids which increased the cholesterol/phospholipid mole ratio. With altered lipid composition, there was a corresponding age-dependent decrease in membrane fluidity, a reduction of Na+, K(+)-ATPase activity, and an overall greater susceptibility to in vitro lipid peroxidation. Furthermore, lipid peroxidation promoted strong modifications of the membrane fluidity, lipid composition, and Na+,K(+)-ATPase activity just as aging did, thus indicating a possible contribution of oxidative damage to ageing processes. The cases studied revealed that the greater responsiveness of old membranes to in vitro lipid peroxidation resulted in the highest degree of membrane alteration, indicating that all pathological states known to promote a peroxidative injury can have even more dramatic consequences when they take place in old brain.

Oxidative Injury of Synapse and Alteration of Antioxidative Defense Systems in Rats, and Its Prevention by Vitamin E

“…permeability and fluidity. This is supported by a previous report in which it was demonstrated in an in vitro study that isolated synaptosomes are peroxidized by the ascorbate-ferrous ion, resulting in a strong modificatioii of synaptic membrane fluidity and lipid compogition [26]. Thus, oxidative stress induces the deterioration of synaptic membrane functions.…”

Influence of Oxidative Stress on Fusion of Pre-Synaptic Plasma Membranes of the Rat Brain with Phosphatidyl Choline Liposomes, and Protective Effect of Vitamin E

“…In fact, the fluidity of synaptic plasma membrane of rats subjected to hyperoxia becomes lower (4). This idea is supported by a previous report which demonstrated in an in vitro study that isolated synaptosomes are peroxidized by ascorbate-ferrous ion, resulting in a strong modification of the membrane fluidity and lipid composition (30). Results from this study imply that fusion of pre-synaptic plasma membranes with neurotransmitter-containing synaptic vesicles does not take place due to a decline in the lipid-mixing of both synaptic vesicles and pre-synaptic membranes caused by hyperoxia.…”

“…Thus, our results indicate for the first time that oxidative damage of the synaptic plasma membranes caused by oxygen-derived ROS may interrupt the lipid-mixing, which is one of the mechanisms of the membrane fusion, due to the formation of lipid peroxides and the modified protein in the membranes, resulting in a decrease in the fluidity of membranes (4,30). Although vitamin E inhibited these abnormal phenomena in this study, other antioxidants have not been assessed for their efficacy on oxidative damage to the synaptic membrane fusion.…”

Heparin protection against Fe2+‐and Cu2+‐mediated oxidation of liposomes

“…The second preparation used phosphatidylcholine from dried egg yolk and was employed in Cu2+-induced oxidation to monitor conjugated-diene formation. The percentage fatty acid compositions of phosphatidylcholine from fresh and dried egg yolk, as determined by gas-chromatography assay [8] …”