EVIDENCE THAT INCREASED HIPPOCAMPAL EXPRESSION OF THE CYTOKINE INTERLEUKIN-1-BETA IS A COMMON TRIGGER FOR AGE-INDUCED AND STRESS-INDUCED IMPAIRMENTS IN LONG-TERM POTENTIATION

Several cytokines and their receptors are identified in brain; one of these is the proinflammatory cytokine interleukin-1 beta that is synth esized and released from neurons and glia in response to stress or ins ult. Among the actions of interleukin-1 beta is its ability to inhibit long-term potentiation in the hippocampus in vitro, an action that mi mics one of the consequences of stress and age. It has been shown that the concentration of interleukin-1 beta in brain tissue is increased in neurodegenerative conditions, and recent evidence from our laborato ry has indicated an increase in the concentration of interleukin-1 bet a in the hippocampus of aged rats. These observations led us to consid er that the underlying common cause of impaired long-term potentiation in aged and stressed rats might be increased endogenous interleukin-1 beta concentration in hippocampus. The data presented here indicate t hat there was an inverse relationship between concentration of interle ukin-1 beta in the dentate gyrus and long-term potentiation in perfora nt path-->granule cell synapses in aged rats, stressed rats, and rats pretreated with interleukin-1 beta. The evidence suggested that the cy tokine induces formation of reactive oxygen species that triggers lipi d peroxidation in vivo, as well as in vitro, and that these changes le ad to depletion of membrane arachidonic acid that correlates with impa ired long-term potentiation. We propose that three theories of aging, the glucocorticoid theory, the membrane theory, and the free radical t heory, constitute three facets of age with one underlying trigger: an increase in the endogenous concentration of interleukin-1 beta in hipp ocampus.