Age-related impairment in long-term potentiation in hippocampus: a role for the cytokine, interleukin-1 beta?
Ageing is associated with impairments in a variety of biological functions, one of the most striking might be considered to be the impairment in cognitive function. This impairment probably relates to the vulnerability of the hippocampus to the ageing process, since several cognitive functions rely on the integrity of this brain area. Analysis of the mechanisms underlying the effect of ageing on hippocampal function has focused to a great extent on analysis of age-related changes in long-term potentiation (LTP) in hippocampus of experimental animals. LTP is a remarkable form of synaptic plasticity which is characterized by a persistent increase in synaptic efficacy following tetanic stimulation of an afferent pathway to one of the hippocampal subfields. On the basis of its properties, LTP has been proposed as a biological substrate for learning and/or memory. There is general agreement that aged rats exhibit an impaired ability to sustain LTP but there is no agreement on the underlying cause of this deficit. In this review, the evidence which suggests that age-related changes in membrane composition, triggered by oxidative changes, might significantly contribute to the impairment in LTP, is considered. These findings are supported by recent data which indicates that dietary supplementation with the antioxidant vitamins, E and C, reversed the age-related impairment in LTP, in parallel with reversing the age-related decrease in alpha-tocopherol concentration and the age-related increase in lipid peroxidation. The possibility that the proinflammatory cytokine, interleukin-1 beta, triggers several age-related changes in hippocampus is considered and, based on the evidence presented, the hypothesis that interleukin-1 beta plays a significant role in ageing in the hippocampus is proposed.
Physiology Department, Trinity College, Dublin, Ireland. lynchma@tcd.ie
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D000375:Aging / Q000502:physiology* / Q000523:psychology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000502:physiology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000503:physiopathology / Q000517:prevention & control; D005231:Fatty Acids, Unsaturated / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development* / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015227:Lipid Peroxidation; D017774:Long-Term Potentiation / Q000502:physiology*; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000502:physiology; D008569:Memory Disorders / Q000178:diet therapy / Q000503:physiopathology* / Q000517:prevention & control; D008959:Models, Neurological; D010740:Phospholipases / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats
D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D007375:Interleukin-1; D008563:Membrane Lipids; D016718:Arachidonic Acid; D018698:Glutamic Acid; D011505:Protein-Tyrosine Kinases; D010740:Phospholipases