Lundbeck Research USA, Neuroinflammation Drug Biology Unit 215 College Road, Paramus, NJ 07652, USA.
Mol Cell Neurosci. 2013 Mar;53:52-62. doi: 10.1016/j.mcn.2012.10.002. Epub 2012 Oct 12.
There is by now substantial clinical evidence for an association between specific mood disorders and altered immune function. More recently, a number of hypotheses have been forwarded to explain how components of the innate immune system can regulate brain function at the cellular and systems levels and how these may underlie the pathology of disorders such as depression, PTSD and bipolar disorder. In this review we draw reference to biochemical, cellular and animal disease models, as well as clinical observations to elucidate the role of the innate immune system in psychiatric disorders. Proinflammatory cytokines, such as IL-1β IL-6 and TNFα, which feature prominently in the immune response to pathogen in the periphery, have unique and specific actions on neurons and circuits within the central nervous system. Effects of these signaling molecules on neurotransmission, memory, and glucocorticoid function, as well as animal behaviors such as social withdrawal and fear conditioning relevant to psychiatric disorders are elucidated. Finally, we highlight future directions for studies, including the use of peripheral biomarkers, relevant for developing new therapeutic approaches for treating psychiatric illnesses. This article is part of Special Issue entitled 'neuroinflammation in neurodegeneration and neurodysfunction'.
现在已经有大量的临床证据表明特定的情绪障碍与免疫功能改变之间存在关联。最近,提出了许多假设来解释先天免疫系统的成分如何在细胞和系统水平上调节大脑功能,以及这些机制如何构成抑郁症、创伤后应激障碍和双相情感障碍等疾病的病理学基础。在这篇综述中,我们参考了生化、细胞和动物疾病模型以及临床观察结果,以阐明先天免疫系统在精神疾病中的作用。在周围对病原体的免疫反应中起重要作用的促炎细胞因子,如白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNFα),对中枢神经系统内的神经元和回路具有独特而特异的作用。这些信号分子对神经传递、记忆和糖皮质激素功能的影响,以及与精神疾病相关的动物行为,如社交回避和恐惧条件反射,都得到了阐明。最后,我们强调了未来的研究方向,包括使用外周生物标志物,这对于开发治疗精神疾病的新治疗方法很有意义。本文是题为“神经退行性和神经功能障碍中的神经炎症”的特刊的一部分。