Deficits in nerve growth factor release and tyrosine receptor kinase phosphorylation are associated with age-related impairment in long-term potentiation in the dentate gyrus

Previous findings have indicated that nerve growth factor may play a role in the expression of long-term potentiation in perforant path–granule cell synapses and that nerve growth factor treatment restores the ability of aged rats to sustain long-term potentiation. In this study, we have attempted to analyse the changes which occur in nerve growth factor release and tyrosine receptor kinase phosphorylation following tetanization in tissue prepared from dentate gyrus of young rats, as well as aged rats which did or did not sustain long-term potentiation. We report that KCl-stimulated nerve growth factor release was significantly increased in slices of the dentate gyrus or whole hippocampus, but not in synaptosomes prepared from the dentate gyrus. KCl-induced nerve growth factor release was also significantly enhanced in slices prepared from tetanized, compared with untetanized, tissue obtained from young rats and aged rats which sustained long-term potentiation; this response was absent in tissue prepared from aged rats which failed to sustain long-term potentiation, perhaps due to the enhanced basal nerve growth factor release observed in this tissue. Tetanization increased tyrosine receptor kinase phosphorylation in the dentate gyrus of young rats and aged rats which sustained long-term potentiation. In parallel with the changes in nerve growth factor release, tyrosine receptor kinase phosphorylation was markedly increased in untetanized tissue, which may contribute to the lack of effect in tetanized tissue prepared from aged rats which failed to sustain long-term potentiation. We observed that nerve growth factor concentration and tyrosine receptor kinase expression were decreased in aged, compared with young, rats.The data suggest that deficits in nerve growth factor release and subsequent signalling may contribute to age-related deficits in long-term potentiation.