Downregulation of IL-4-induced signalling in hippocampus contributes to deficits in LTP in the aged rat
Downregulation of IL-4-induced signalling in hippocampus contributes to deficits in LTP in the aged rat
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DOI：
10.1016/j.neurobiolaging.2004.07.002
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发表时间：
2005-05-01
影响因子：
4.2
通讯作者：
Lynch, MA
中科院分区：
文献类型：
--
作者：
Maher, FO;Nolan, Y;Lynch, MA
衰老的特征在于学习和记忆的缺陷以及海马体中长时程增强（LTP）的缺陷。一些与年龄相关的变化，包括钙稳态机制的功能障碍和炎症过程的上调可能有助于这些缺陷。在这里，我们利用了这样一个事实，即老年大鼠分为一个亚组，未能维持UP的穿通路径颗粒细胞突触作为强直刺激的结果，和一个亚组，维持UP的方式无法区分从年轻的大鼠，在努力确定两个亚组的差异变化。IL-1 β浓度和IL-1 β诱导信号的年龄相关性增加在未能维持LTP的老年大鼠中更为深刻。我们证明，功能性IL-4受体在大鼠海马中表达，并且年龄与IL-4浓度的降低相关，伴随着JAK-1和STAT-6磷酸化的降低。我们认为，促炎和抗炎细胞因子之间的不平衡，在老年人的大脑显着有助于与年龄相关的突触功能的缺陷。(C)2004年爱思唯尔公司All rights reserved.
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 UP in perforant path granule cell synapses as a result of tetanic stimulation, and a subgroup which sustains UP 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. (C) 2004 Elsevier Inc. All rights reserved.