Pickering Mark, O'Connor John J
UCD School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Prog Brain Res. 2007;163:339-54. doi: 10.1016/S0079-6123(07)63020-9.
The older notion of a central nervous system existing in essential isolation from the immune system has changed dramatically in recent years as the body of evidence relating to the interactions between these two systems has grown. Here we address the role of a particular subset of immune modulatory molecules, the pro-inflammatory cytokines, in regulating neuronal function and viability in the dentate gyrus of the hippocampus. These inflammatory mediators are known to be elevated in many neuropathological conditions, such as Alzheimer's disease, Parkinson's disease and ischaemic injury that follows stroke. Pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta) and interleukin 18 (IL-18), have been shown to regulate neurotoxicity; although, due to the complexity of the cytokine action in neurons and glia, the effect may be either facilitatory or protective, depending on the circumstances. As well as their role in neurotoxicity and neuroprotection, the pro-inflammatory cytokines have also been shown to be potent regulators of synaptic function. In particular, TNF-alpha, IL-1beta and IL-18 have all been shown to inhibit long-term potentiation, a form of neuronal plasticity widely believed to underlie learning and memory, both in the early p38 mitogen activated protein kinase-dependant phase and the later protein synthesis-dependant phase. In this article we address the mechanisms underlying these cytokine effects in the dentate gyrus of the hippocampus.
近年来，随着有关这两个系统之间相互作用的证据越来越多，认为中枢神经系统与免疫系统基本隔离的旧观念已发生了巨大变化。在此，我们探讨免疫调节分子的一个特定子集——促炎细胞因子，在调节海马齿状回中神经元功能和生存能力方面的作用。已知这些炎症介质在许多神经病理状况下会升高，如阿尔茨海默病、帕金森病以及中风后的缺血性损伤。促炎细胞因子，如肿瘤坏死因子-α（TNF-α）、白细胞介素1-β（IL-1β）和白细胞介素18（IL-18），已被证明可调节神经毒性；不过，由于细胞因子在神经元和神经胶质细胞中的作用复杂，其效果可能是促进性的，也可能是保护性的，这取决于具体情况。除了在神经毒性和神经保护方面的作用外，促炎细胞因子还被证明是突触功能的有效调节因子。特别是，TNF-α、IL-1β和IL-18均已被证明在早期p38丝裂原活化蛋白激酶依赖性阶段和后期蛋白质合成依赖性阶段均可抑制长时程增强，长时程增强是一种广泛认为是学习和记忆基础的神经元可塑性形式。在本文中，我们探讨这些细胞因子在海马齿状回中的作用机制。
