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 include s a decrease in membrane polyunsaturated fatty acids, including arachi donic acid, and an increase in membrane cholesterol. Alterations in me mbrane structure are likely to impact on transmitter release, which re lies on the fusion of synaptic plasma and synaptic vesicle membranes, and it may therefore be the underlying cause of the age-related decrea se in glutamate release in hippocampal preparations. Recent evidence i ndicates that interleukin-1, by binding with its receptor, inhibits gl utamate release in hippocampal synaptosomes prepared from young but no t aged rats. The age related attenuated effect may be due to impaired ligand-receptor interactions arising from the change in membrane compo sition, 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 a cid and its precursor, gamma-linolenic acid; on membrane arachidonic a cid concentration glutamate release and on the release response to int erleukin-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-1 beta. We also pres ent data that indicate that the age-related decrease in glutamate rele ase from hippocampal synaptosomes was reversed in aged animals that ha d been fed on the experimental diet. The data support the view that ch anges in membrane composition contribute to certain age-related defici ts, in particular the decrease in glutamate release observed in hippoc ampal synaptosomes. (C) 1998 Elsevier Science Inc.