Depino Amaicha M, Alonso Mariana, Ferrari Carina, del Rey Adriana, Anthony Daniel, Besedovsky Hugo, Medina Jorge H, Pitossi Fernando
Fundación Instituto Leloir, UBA-CONICET, Buenos Aires, Argentina.
Hippocampus. 2004;14(4):526-35. doi: 10.1002/hipo.10164.
The interleukin-1 (IL-1) cytokine family (IL-1alpha, IL-beta, and the IL-1 receptor antagonist) is involved in immune and inflammatory responses both in the brain and in the periphery. Recently, it has also been shown to influence behavior and memory consolidation. However, within the experimental systems studied, it has remained unclear whether the role of IL-1beta is associated solely with a pathophysiological process or whether it is a neuromodulator in normal adult brain. To evaluate the involvement of the nonpathological endogenous IL-1 system in learning, we studied the expression of IL-1alpha, IL-1beta, and IL-1ra during memory consolidation. We observed a learning-specific hippocampal IL-1alpha mRNA induction, but not that of IL-1beta or IL-1ra mRNAs, after inhibitory avoidance training. Moreover, when IL-1 receptor activity was inhibited using an adenoviral vector that expresses the IL-1 receptor antagonist (IL-1ra) in the hippocampus, both short-term and long-term memory retention scores were facilitated. In contrast, endogenous hippocampal IL-1 played no role in the habituation to a novel environment. These results demonstrate that endogenous hippocampal IL-1 specifically modulates a fear-motivated learning task, and suggest that IL-1alpha activity in the CNS is part of the hippocampal memory processing.
白细胞介素-1（IL-1）细胞因子家族（IL-1α、IL-β和IL-1受体拮抗剂）参与大脑和外周的免疫及炎症反应。最近，研究还表明它会影响行为和记忆巩固。然而，在所研究的实验系统中，IL-1β的作用究竟是仅与病理生理过程相关，还是在正常成年大脑中作为一种神经调节剂，仍不清楚。为了评估非病理性内源性IL-1系统在学习中的作用，我们研究了记忆巩固过程中IL-1α、IL-1β和IL-1ra的表达。在抑制性回避训练后，我们观察到海马体中存在学习特异性的IL-1α mRNA诱导，但未观察到IL-1β或IL-1ra mRNA的诱导。此外，当使用在海马体中表达IL-1受体拮抗剂（IL-1ra）的腺病毒载体抑制IL-1受体活性时，短期和长期记忆保持分数均得到提高。相反，内源性海马体IL-1在对新环境的习惯化过程中不起作用。这些结果表明，内源性海马体IL-1特异性调节恐惧驱动的学习任务，并提示中枢神经系统中IL-1α的活性是海马体记忆处理的一部分。
