Pozzi Davide, Menna Elisabetta, Canzi Alice, Desiato Genni, Mantovani Cristina, Matteoli Michela
Department of Biomedical Sciences, Humanitas University, Rozzano, Italy.
Humanitas Clinical and Research Center, Rozzano, Italy.
Front Mol Neurosci. 2018 Apr 5;11:111. doi: 10.3389/fnmol.2018.00111. eCollection 2018.
In the last 15 years, groundbreaking genetic progress has underlined a convergence onto coherent synaptic pathways for most psychiatric and neurodevelopmental disorders, which are now collectively called "synaptopathies." However, the modest size of inheritance detected so far indicates a multifactorial etiology for these disorders, underlining the key contribution of environmental effects to them. Inflammation is known to influence the risk and/or severity of a variety of synaptopathies. In particular, pro-inflammatory cytokines, produced and released in the brain by activated astrocytes and microglia, may play a pivotal role in these pathologies. Although the link between immune system activation and defects in cognitive processes is nowadays clearly established, the knowledge of the molecular mechanisms by which inflammatory mediators specifically hit synaptic components implicated in synaptopathies is still in its infancy. This review summarizes recent evidence showing that the pro-inflammatory cytokine interleukin-1β (IL-1β) specifically targets synaptopathy molecular substrate, leading to memory defects and pathological processes. In particular, we describe three specific pathways through which IL-1β affects (1) synaptic maintenance/dendritic complexity, (2) spine morphology, and (3) the excitatory/inhibitory balance. We coin the term immune synaptopathies to identify this class of diseases.
在过去15年里，具有开创性的遗传学进展突显了大多数精神疾病和神经发育障碍在连贯的突触通路方面的趋同性，这些疾病现在统称为“突触病”。然而，迄今为止检测到的遗传效应规模较小，表明这些疾病具有多因素病因，突显了环境因素对它们的关键作用。已知炎症会影响多种突触病的风险和/或严重程度。特别是，由活化的星形胶质细胞和小胶质细胞在大脑中产生和释放的促炎细胞因子，可能在这些病理过程中起关键作用。尽管如今免疫系统激活与认知过程缺陷之间的联系已明确确立，但对于炎症介质如何特异性作用于突触病相关突触成分的分子机制，我们的了解仍处于起步阶段。本综述总结了近期证据，表明促炎细胞因子白细胞介素-1β（IL-1β）特异性作用于突触病分子底物，导致记忆缺陷和病理过程。特别是，我们描述了IL-1β影响（1）突触维持/树突复杂性、（2）棘突形态以及（3）兴奋性/抑制性平衡的三条特定途径。我们创造了“免疫突触病”这一术语来识别这类疾病。
