Age-related impairment in LTP is accompanied by enhanced activity of stress-activated protein kinases: analysis of underlying mechanisms.
The age-related impairment in long-term potentiation in the rat dentate gyrus is coupled with an increase in the proinflammatory cytokine, interleukin-1beta (IL-1beta). It is possible that this increase in IL-1beta might be a consequence of the age-related increase in reactive oxygen species production in hippocampal tissue. In this study we set out to identify the underlying cause of the age-related increase in reactive oxygen species production and to establish whether any consequences of such a change might impact on the ability of aged rats to sustain long-term potentiation (LTP). We report that there was an age-related increase in the activity of superoxide dismutase but no parallel increases in activities of glutathione peroxidase or catalase, while age-related decreases in the concentration of the scavengers, vitamins E and C and glutathione were also observed. We propose that these compromises in antioxidative strategies may result in an increase in reactive oxygen species production. The data described indicate that IL-1beta and H2O2 increase the activity of two stress-activated mitogen-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 in vitro, while age-related increases in both kinases were observed. We propose that the endogenous increase in these parameters which occurs with age induces the increase in activity of the stress-activated kinases, which in turn impacts on the ability of the aged rat to sustain LTP.
O'Donnell
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Department of Physiology, Trinity College, Dublin 2, Ireland.
Vereker
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Lynch
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MA
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D018891:Dentate Gyrus / Q000254:growth & development / Q000502:physiology*; D019587:Dietary Supplements; D004558:Electric Stimulation; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D007375:Interleukin-1; D017382:Reactive Oxygen Species; D014810:Vitamin E; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D001205:Ascorbic Acid