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Neurobiol Aging. 2005 May;26(5):717-28.

Downregulation of IL-4-induced signalling in hippocampus contributes to deficits in LTP in the aged rat.

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1
Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.

Abstract

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.

[Indexed for MEDLINE]

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