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The age‐related increase in IL‐1 type I receptor in rat hippocampus is coupled with an increase in caspase‐3 activation
Author(s) -
Lynch Aileen M.,
Lynch Marina A.
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02012.x
Subject(s) - p38 mitogen activated protein kinases , microbiology and biotechnology , biology , receptor , colocalization , caspase 1 , kinase , medicine , endocrinology , chemistry , protein kinase a , biochemistry , inflammasome
Evidence from several studies indicates that expression of interleukin‐1β (IL‐1β) and IL‐1 type I receptor is particularly high in hippocampus, and it has recently been shown that the concentration of IL‐1β 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‐1β‐induced increase in caspase‐3 activity was abrogated by the p38 inhibitor, SB203580. The IL‐1β‐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.