Networking into neural plasticity: a rising score on the cytokine learning curve.
Networking into neural plasticity: a rising score on the cytokine learning curve.
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神经可塑性网络：细胞因子学习曲线上的得分不断上升。
DOI：
10.1016/j.bbi.2013.06.008
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Quan,Ning
中科院分区：
文献类型：
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作者：
Quan,Ning
自从发现炎性细胞因子以来，细胞因子作用的触角已经慢慢地越过免疫系统的边界进入中枢神经系统（CNS），在那里它们似乎出乎意料地移植到这个炎症厌恶的环境中。在感染或损伤的CNS组织中可以明显地发现细胞因子活性，因为在这些特殊情况下需要它们在介导免疫活性和伤口愈合中的传统作用。开始引起兴趣的是早期发现，即未受伤和未感染的CNS中的细胞因子介导外周炎症期间的疾病行为和神经内分泌激活，表明这些分子具有神经调节作用（Quan和Banks，2007）。细胞因子作用的最远延伸是这样的概念，即它们甚至可以参与正常的脑生理学，而在脑或外周中没有可检测到的炎症。这方面的一系列研究已经由本期BBI中关于细胞因子网络和学习的研究的作者开创（德尔雷等人，他们的开场白是白细胞介素-1（IL-1）参与长时程增强（LTP）的开创性证明，LTP是许多形式的学习和记忆中的一个完整的细胞过程（Schneider et al.，1998年）。他们发现IL-1的表达在LTP期间显著增加。此外，阻断IL-1活性导致可逆的LTP抑制，而使用神经递质拮抗剂阻断LTP的诱导可防止IL-1的诱导。因此，IL-1被证明是由CNS细胞产生的神经元活性诱导的，并在调节学习和记忆中至关重要的细胞过程中发挥作用。重要的是，在这项研究中发现IL-1支持LTP，而许多其他研究发现相反（Deak，2007）。Yirmiya等人对这种明显的二分法进行了解释，他认为大多数研究使用病理生理条件诱导高水平的IL-1。高浓度的IL-1往往会阻碍学习和记忆，但生理IL-1在大脑中以低水平产生，支持正常的学习和记忆过程（Yirmiya和Goshen，2011）。事实上，已经发现另一种细胞因子IL-6的不同作用，其负面影响LTP（Balschun等人，2004），不同于在病理生理条件下经常观察到的IL-1和IL-6之间的典型协同作用。
Ever since the discovery of inflammatory cytokines, the tentacles of cytokine actions have slowly crept beyond the boundaries of the immune system into the central nervous system (CNS) where they have unexpectedly seemed to graft onto this inflammation-aversive environment. Cytokine activity can obviously be found in infected or injured CNS tissue as their traditional roles in mediating immune activity and wound healing are needed under these special circumstances. What began to intrigue were early findings that cytokines in the un-injured and un-infected CNS mediate sickness behavior and neuroendocrine activation during peripheral inflammation, indicating a neuromodulatory role for these molecules (Quan and Banks, 2007). The furthest extension for the role of cytokines is the notion that they may even be involved in normal brain physiology without precedent detectable inflammation either in the brain or in the periphery. A line of research in this regard has been pioneered by the authors of the study on cytokine network and learning in this issue of BBI (Del Rey et al., 2013), culminating to their demonstration of a cytokine network in the physiological process of learning.Their opening salvo was the seminal demonstration of the involvement of interleukin-1 (IL-1) in long-term potentiation (LTP), an integral cellular process in many forms of learning and memory (Schneider et al., 1998). They found the expression of IL-1 is significantly increased during LTP. Furthermore, blocking IL-1 activity resulted in a reversible inhibition of LTP, whereas blocking the induction of LTP using a neurotransmitter antagonist prevented the induction of IL-1. Thus, IL-1 was shown to be induced by neuronal activity, produced from cells of the CNS, and played a role in the regulation of a cellular process that is critical in learning and memory. Importantly, IL-1 was found to support LTP in this study, whereas the opposite was found by many other studies (Deak, 2007). An explanation for this apparent dichotomy was furnished by Yirmiya et al. who suggested most studies used pathophysiological conditions to induce high levels of IL-1. High IL-1 concentrations tend to impede learning and memory, but physiological IL-1 is produced at low levels in the brain, supporting normal learning and memory processes (Yirmiya and Goshen, 2011). Indeed, distinct actions have been found for another cytokine, IL-6, which negatively influences LTP (Balschun et al., 2004) under physiological conditions, unlike the typical synergism between IL-1 and IL-6 often observed under pathophysiological conditions.