Downregulation of IL-4-induced signalling in hippocampus contributes to deficits in LTP in the aged rat.
Ageing is characterized by deficits in learning and memory and by a deficit in long-term potentiation (LTP) in hippocampus. Several age-related changes, including dysfunction of calcium homeostatic mechanisms and upregulation of inflammatory processes are likely to contribute to these deficits. Here we exploited the fact that aged rats fall into a subgroup which fail to sustain LTP in perforant path granule cell synapses as a result of tetanic stimulation, and a subgroup which sustains LTP in a manner indistinguishable from young rats, in an effort to identify differential changes in the two subgroups. The age-related increase in IL-1beta concentration and IL-1beta-induced signalling was more profound in aged rats which failed to sustain LTP. We demonstrate that functional IL-4 receptors are expressed in rat hippocampus and that age is associated with a decrease in IL-4 concentration accompanied by a decrease in phosphorylation of JAK-1 and STAT-6. We propose that the imbalance between pro-inflammatory and anti-inflammatory cytokines in the aged brain significantly contributes to age-related deficits in synaptic function.
Maher
F O
FO
Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.
Nolan
Yvonne
Y
Lynch
Marina A
MA
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D007375:Interleukin-1 / Q000032:analysis / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019948:Receptors, Interleukin-4 / Q000378:metabolism
D007375:Interleukin-1; D020382:Interleukin-18; D016755:Proto-Oncogene Proteins c-jun; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D020928:Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases