A dual role for interleukin-1 in hippocampal-dependent memory processes
A dual role for interleukin-1 in hippocampal-dependent memory processes
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DOI：
10.1016/j.psyneuen.2007.09.004
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发表时间：
2007-09-01
影响因子：
3.7
通讯作者：
Yirmiya, Raz
中科院分区：
文献类型：
--
作者：
Goshen, Inbal;Kreisel, Tirzah;Yirmiya, Raz
大量研究表明，促炎细胞因子白细胞介素-1（IL-1）的病理生理水平对记忆功能产生有害影响。然而，最近的证据表明，IL-1可能是正常生理所必需的。调节依赖于大脑的记忆。为了证实IL-1在学习和记忆中的生理作用，我们研究了学习经历后IL-1基因表达的诱导，以及通过遗传或药理学操作阻断IL-1信号传导对记忆功能的影响。我们发现，IL-1基因表达诱导海马24小时后，在野生型小鼠的恐惧条件，但不是在两个小鼠品系与受损的IL-1信号。此外，我们报告说，转基因过表达的IL-1受体拮抗剂限制到中枢神经系统（1 L-1 raTG）的小鼠显示受损的大脑皮层依赖性和完整的大脑皮层非依赖性的记忆在水迷宫和恐惧条件范例。我们进一步证明，在产前发育过程中通过渗透压微泵连续给予IL-1 ra会破坏成年小鼠的记忆表现，这表明IL-1不仅在海马依赖性记忆的形成中起着关键作用，而且在正常的海马发育中也起着关键作用。最后，我们通过在学习后脑室内（ICV）给予不同剂量的IL-1 β和IL-1 ra来测试IL-1在记忆中的双重作用，提供了第一个系统性证据，即IL-1参与海马依赖性记忆遵循倒U形模式，即，脑IL-1水平的轻微增加可以改善记忆，而任何偏离生理。通过IL-1水平的过度升高或通过IL-1信号传导的阻断，导致记忆受损。(C)2007爱思唯尔有限公司版权所有。
Ample research demonstrates that pathophysiological levels of the pro-inflammatory cytokine interleukin-1 (IL-1) produces detrimental effects on memory functioning. However, recent evidence suggests that IL-1 may be required for the normal physiological. regulation of hippocampal-dependent memory. To substantiate the physiological rote of IL-1 in learning and memory we examined the induction of IL-1 gene expression following a learning experience, and the effects of IL-1 signaling blockade, by either genetic or pharmacological manipulations, on memory functioning. We show that IL-1 gene expression is induced in the hippocampus 24h following fear-conditioning in wild type mice, but not in two mouse strains with impaired IL-1 signaling. Moreover, we report that mice with transgenic over-expression of IL-1 receptor antagonist restricted to the CNS (1L-1raTG) display impaired hippocampal-dependent and intact hippocampal-independent memory in the water maze and fear-conditioning paradigms. We further demonstrate that continuous administration of IL-1ra via osmotic minipumps during prenatal development disrupt memory performance in adult mice, suggesting that IL-1 plays a critical role not only in the formation of hippocampal-dependent memory but also in normal hippocampal development. Finally, we tested the dual role of IL-1 in memory by intracerebroventricular (ICV) administration of different doses of 1L-1 beta and IL-1ra following learning, providing the first systematic evidence that the involvement of IL-1 in hippocampal-dependent memory follows an inverted U-shaped pattern, i.e., a slight increase in brain IL-1 levels can improve memory, whereas any deviation from the physiological. range, either by excess elevation in IL-1 levels or by blockade of IL-1 signaling, results in impaired memory. (C) 2007 Elsevier Ltd. All rights reserved.