The ability of aged rats to sustain long-term potentiation is restored when the age-related decrease in membrane arachidonic acid concentration is reversed.

The ability of aged rats to sustain long-term potentiation in the dentate gyrus of the hippocampus is impaired and this impairment correlates with decreased release of glutamate and a decrease in membrane arachidonic acid concentration. Twenty-two-month-old rats receiving a diet supplemented with arachidonic acid and its precursor, gamma-linolenic acid, sustained long-term potentiation in a manner indistinguishable from four-month-old controls. Dietary supplementation also restored arachidonic acid concentrations in membranes prepared from hippocampus of these aged animals to levels observed in hippocampus of four-month-old rats. Glutamate release stimulated by depolarization was similar in dentate gyrus prepared from young rats and aged rats which received the experimental diet, but was markedly reduced in aged animals which received the control diet. In addition, the synergism between arachidonic acid and the metabotropic glutamate receptor agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate, on glutamate release, which was observed in hippocampal synaptosomes prepared from four-month-old rats, was also observed in hippocampal preparations obtained from aged rats which had been fed with the experimental diet, but was absent in hippocampal preparations obtained from aged animals which were fed with control diet. Thus, reversing the age-related decrease in membrane arachidonic acid concentration restored ability of aged animals to sustain long-term potentiation and reversed age-related changes in glutamate release.