Konefal Sarah C, Stellwagen David
Department of Neurology and Neurosurgery, Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada H3G 1A4.
Department of Neurology and Neurosurgery, Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada H3G 1A4
Philos Trans R Soc Lond B Biol Sci. 2017 Mar 5;372(1715). doi: 10.1098/rstb.2016.0160.
The proinflammatory cytokine tumour necrosis factor-alpha (TNFα) has long been characterized for its role in the innate immune system, but more recently has been found to have a distinct role in the nervous system that does not overlap with other proinflammatory cytokines. Through regulation of neuronal glutamate and GABA receptor trafficking, TNF mediates a homeostatic form of synaptic plasticity, but plays no direct role in Hebbian forms of plasticity. As yet, there is no evidence to suggest that this adaptive plasticity plays a significant role in normal development, but it does maintain neuronal circuit function in the face of several types of disruption. This includes developmental plasticity in primary sensory cortices, as well as modulating the response to antidepressants, chronic antipsychotics and drugs of abuse. TNF is also a prominent component of the neuroinflammation occurring in most neuropathologies, but the role of TNF-mediated synaptic plasticity in this context remains to be determined. We tested this in a maternal immune activation (MIA) model of neurodevelopmental disorders. Using TNF mice, we observed that TNF is not required for the expression of abnormal social or anxious behaviour in this model. This indicates that TNF does not uniquely contribute to the development of neuronal dysfunction in this model, and suggests that during neuroinflammatory events, compensation between the various proinflammatory cytokines is the norm.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.
促炎细胞因子肿瘤坏死因子-α（TNFα）长期以来因其在先天免疫系统中的作用而被人们所熟知，但最近发现它在神经系统中具有独特作用，且与其他促炎细胞因子不存在重叠。通过调节神经元谷氨酸和γ-氨基丁酸（GABA）受体的转运，TNF介导一种稳态形式的突触可塑性，但在赫布型可塑性中不发挥直接作用。目前，尚无证据表明这种适应性可塑性在正常发育中起重要作用，但它确实能在面对多种类型的破坏时维持神经元回路功能。这包括初级感觉皮层的发育可塑性，以及调节对抗抑郁药、慢性抗精神病药和滥用药物的反应。TNF也是大多数神经病理学中发生的神经炎症的一个重要组成部分，但在这种情况下，TNF介导的突触可塑性的作用仍有待确定。我们在神经发育障碍的母体免疫激活（MIA）模型中对此进行了测试。使用TNF基因敲除小鼠，我们观察到在该模型中，异常社交或焦虑行为的表达并不需要TNF。这表明TNF并非该模型中神经元功能障碍发展的唯一因素，这也提示在神经炎症事件中，各种促炎细胞因子之间的代偿是常态。本文是主题为“整合赫布型可塑性和稳态可塑性”特刊的一部分。
