The age-related increase in IL-1 type I receptor in rat hippocampus is coupled with an increase in caspase-3 activation.
Evidence from several studies indicates that expression of interleukin-1beta (IL-1beta) and IL-1 type I receptor is particularly high in hippocampus, and it has recently been shown that the concentration of IL-1beta is increased in the hippocampus of the aged rat. Here we report that this increase is coupled with an increase in expression of IL-1 type I receptor and increased activity of IL-1 receptor-associated kinase. The evidence presented indicates that the age-related increase in activity of the mitogen-activated protein kinases, Jun N-terminal kinase (JNK) and p38, was accompanied by enhanced caspase-3 activity. Analysis of colocalization of activated caspase-3 with activated p38 (p-p38) suggested that p-p38 was necessary for activation of caspase-3; while in vitro analysis indicated that the IL-1beta-induced increase in caspase-3 activity was abrogated by the p38 inhibitor, SB203580. The IL-1beta-induced increase in caspase-3 activity in vitro was also abrogated by vasoactive intestinal peptide, which is a JNK inhibitor; however, colocalization of activated JNK (p-JNK) and activated caspase-3 did not clearly identify JNK as an upstream activator of caspase-3. We propose that these changes are indicative of cell death in aged hippocampus and suggest that they contribute to the age-related decrease in long-term potentiation in perforant path granule cell synapses.
Lynch
Aileen M
AM
Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin 2, Ireland. amlynch@tcd.ie
Lynch
Marina A
MA
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D017774:Long-Term Potentiation / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019580:Perforant Pathway / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases