Age-related changes in synaptic function: Analysis of the effect of dietary supplementation with omega-3 fatty acids

Depolarization-induced transmitter release in synaptosomes prepared from th e hippocampus of aged rats is decreased compared with release from young an imals. Although the underlying cause of this deficit is not known, some evi dence suggests that increased membrane rigidity may contribute to these age -related synaptic changes. One possible consequence of the decreased transm itter release in the hippocampus of aged rats is a reduced ability to susta in long-term potentiation in perforant path-granule cell synapses, a pathwa y in which maintenance of long-term potentiation and increased glutamate re lease have been coupled. The observation that there is an age-dependent imp airment in long-term potentiation is consistent with this view. If the age- related deficits in release and long-term potentiation are a consequence of increased membrane rigidity, it must be predicted that any manoeuvre which reverses membrane rigidity should reverse these functional deficits. In th e present study, we investigated the effect of dietary manipulation of aged rats with omega-3 fatty acids on synaptic function. The data obtained indicate that an eight-week modified feeding schedule rev ersed the age-related impairments in long-term potentiation and depolarizat ion-induced glutamate transmitter release. We also report that the concentr ations of both docosahexanoic acid and arachidonic acid, two main polyunsat urated fatty acids in neuronal membranes, were decreased in the hippocampus of aged rats, and were restored by dietary manipulation. The data are cons istent with the hypothesis that these deficits results from a change in mem brane composition. (C) 1999 IBRO. Published by Elsevier Science Ltd.