Analysis of the effect of membrane arachidonic acid concentration on modulation of glutamate release by interleukin-1: an age-related study.

Aging is associated with a change in membrane composition that includes a decrease in membrane polyunsaturated fatty acids, including arachidonic acid, and an increase in membrane cholesterol. Alterations in membrane structure are likely to impact on transmitter release, which relies on the fusion of synaptic plasma and synaptic vesicle membranes, and it may therefore be the underlying cause of the age-related decrease in glutamate release in hippocampal preparations. Recent evidence indicates that interleukin-1, by binding with its receptor, inhibits glutamate release in hippocampal synaptosomes prepared from young but not aged rats. The age-related attenuated effect may be due to impaired ligand-receptor interactions arising from the change in membrane composition, which should theoretically be reversed by increasing membrane polyunsaturated fatty acid concentration. To test this hypothesis, we have investigated the effect of a diet supplemented with arachidonic acid and its precursor, gamma-linolenic acid, on membrane arachidonic acid concentration, glutamate release and on the release response to interleukin-1 in hippocampal tissue prepared from aged and young rats. We report that dietary supplementation reversed the age-related changes in membrane arachidonic acid and expression of IL-1beta. We also present data that indicate that the age-related decrease in glutamate release from hippocampal synaptosomes was reversed in aged animals that had been fed on the experimental diet. The data support the view that changes in membrane composition contribute to certain age-related deficits, in particular the decrease in glutamate release observed in hippocampal synaptosomes.