Mattei Daniele, Notter Tina
Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, UK.
Curr Top Behav Neurosci. 2020;44:9-34. doi: 10.1007/7854_2018_83.
The hypothesis that the neuroimmune system plays a role in the pathogenesis of different psychiatric disorders, including schizophrenia, depression, and bipolar disease, has attained increasing interest over the past years. Previously thought to have the sole purpose of protecting the central nervous system (CNS) from harmful stimuli, it is now known that the central immune system is critically involved in regulating physiological processes including neurodevelopment, synaptic plasticity, and circuit maintenance. Hence, alterations in microglia - the main immune cell of the CNS - and/or inflammatory factors do not unequivocally connote ongoing neuroinflammation or neuroinflammatory processes per se but rather might signify changes in brain homoeostasis. Despite this, psychiatric research tends to equate functional changes in microglia or alterations in other immune mediators with neuroinflammation. It is the main impetus of this chapter to overcome some of the current misconceptions and possible oversimplifications with respect to neuroinflammation and microglia activity in psychiatry. In order to do so, we will first provide an overview of the basic concepts of neuroinflammation and neuroinflammatory processes. We will then focus on microglia with respect to their ontogeny and immunological and non-immunological functions presenting novel insights on how microglia communicate with other cell types of the central nervous system to ensure proper brain functioning. And lastly, we will delineate the non-immunological functions of inflammatory cytokines in order to address the possible misconception of equating alterations in central cytokine levels with ongoing central inflammation. We hereby hope to help unravel the functional relevance of neuroimmune dysfunctions in psychiatric illnesses and provide future research directions in the field of psychoneuroimmunology.
神经免疫系统在包括精神分裂症、抑郁症和双相情感障碍在内的不同精神疾病发病机制中发挥作用这一假说,在过去几年中受到了越来越多的关注。中枢免疫系统以前被认为唯一的功能是保护中枢神经系统(CNS)免受有害刺激,现在已知它在调节包括神经发育、突触可塑性和神经回路维持等生理过程中起着关键作用。因此,小胶质细胞(中枢神经系统的主要免疫细胞)和/或炎症因子的改变并不明确意味着正在进行的神经炎症或神经炎症过程本身,而可能表明脑内稳态的变化。尽管如此,精神科研究倾向于将小胶质细胞的功能变化或其他免疫介质的改变等同于神经炎症。本章的主要目的是克服目前在精神科领域关于神经炎症和小胶质细胞活动的一些误解和可能的过度简化。为了做到这一点,我们将首先概述神经炎症和神经炎症过程的基本概念。然后,我们将重点关注小胶质细胞的个体发生、免疫和非免疫功能,介绍关于小胶质细胞如何与中枢神经系统的其他细胞类型相互作用以确保大脑正常功能的新见解。最后,我们将阐述炎性细胞因子的非免疫功能,以解决将中枢细胞因子水平改变等同于正在进行的中枢炎症这一可能的误解。我们希望借此帮助揭示神经免疫功能障碍在精神疾病中的功能相关性,并为精神神经免疫学领域提供未来的研究方向。