Weber Michael D, Godbout Jonathan P, Sheridan John F
Division of Biosciences, The Ohio State University, Columbus, OH, USA.
Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH, USA.
Neuropsychopharmacology. 2017 Jan;42(1):46-61. doi: 10.1038/npp.2016.102. Epub 2016 Jun 20.
Mounting evidence indicates that proinflammatory signaling in the brain affects mood, cognition, and behavior and is linked with the etiology of psychiatric disorders, including anxiety and depression. The purpose of this review is to focus on stress-induced bidirectional communication pathways between the central nervous system (CNS) and peripheral immune system that converge to promote a heightened neuroinflammatory environment. These communication pathways involve sympathetic outflow from the brain to the peripheral immune system that biases hematopoietic stem cells to differentiate into a glucocorticoid-resistant and primed myeloid lineage immune cell. In conjunction, microglia-dependent neuroinflammatory events promote myeloid cell trafficking to the brain that reinforces stress-related behavior, and is argued to play a role in stress-related psychiatric disorders. We will discuss evidence implicating a key role for endothelial cells that comprise the blood-brain barrier in propagating peripheral-to-central immune communication. We will also discuss novel neuron-to-glia communication pathways involving endogenous danger signals that have recently been argued to facilitate neuroinflammation under various conditions, including stress. These findings help elucidate the complex communication that occurs in response to stress and highlight novel therapeutic targets against the development of stress-related psychiatric disorders.
越来越多的证据表明，大脑中的促炎信号会影响情绪、认知和行为，并与包括焦虑和抑郁在内的精神疾病的病因有关。本综述的目的是聚焦于应激诱导的中枢神经系统（CNS）与外周免疫系统之间的双向通信通路，这些通路共同作用以促进神经炎症环境的加剧。这些通信通路包括从大脑到外周免疫系统的交感神经输出，它使造血干细胞偏向分化为对糖皮质激素耐药且已致敏的髓系免疫细胞。与此同时，小胶质细胞依赖的神经炎症事件促进髓系细胞向大脑的迁移，这强化了与应激相关的行为，并被认为在与应激相关的精神疾病中起作用。我们将讨论有关内皮细胞在传播外周到中枢免疫通信中起关键作用的证据，内皮细胞构成了血脑屏障。我们还将讨论涉及内源性危险信号的新型神经元到胶质细胞的通信通路，最近有人认为这些通路在包括应激在内的各种条件下促进神经炎症。这些发现有助于阐明应激反应中发生的复杂通信，并突出针对与应激相关的精神疾病发展的新型治疗靶点。
