Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Department of Neurobiology, Duke University, Durham, NC, USA.
Curr Top Behav Neurosci. 2022;53:55-78. doi: 10.1007/7854_2021_242.
From embryonic neuronal migration to adolescent circuit refinement, the immune system plays an essential role throughout central nervous system (CNS) development. Immune signaling molecules serve as a common language between the immune system and CNS, allowing them to work together to modulate brain function both in health and disease. As the resident CNS macrophage, microglia comprise the majority of immune cells in the brain. Much like their peripheral counterparts, microglia survey their environment for pathology, clean up debris, and propagate inflammatory responses when necessary. Beyond this, recent studies have highlighted that microglia perform a number of complex tasks during neural development, from directing neuronal and axonal positioning to pruning synapses, receptors, and even whole cells. In this chapter, we discuss this literature within the framework that immune activation during discrete windows of neural development can profoundly impact brain function long-term, and thus the risk of neurodevelopmental and neuropsychiatric disorders. In this chapter, we review three sensitive developmental periods - embryonic wiring, early postnatal synaptic pruning, and adolescent circuit refinement - in order to highlight the diversity of functions that microglia perform in building a brain. In reviewing this literature, it becomes obvious that timing matters, perhaps more so than the nature of the immune activation itself; largely conserved patterns of microglial response to diverse insults result in different functional impacts depending on the stage of brain maturation at the time of the challenge.
从胚胎神经元迁移到青少年时期的回路细化，免疫系统在中枢神经系统 (CNS) 发育过程中起着至关重要的作用。免疫信号分子是免疫系统和中枢神经系统之间的通用语言，使它们能够共同调节大脑在健康和疾病状态下的功能。作为中枢神经系统中的常驻巨噬细胞，小胶质细胞构成了大脑中大多数免疫细胞。与它们的外周对应物非常相似，小胶质细胞会在环境中检测病理，清理碎片，并在必要时引发炎症反应。除此之外，最近的研究还强调了小胶质细胞在神经发育过程中执行许多复杂的任务，从指导神经元和轴突定位到修剪突触、受体，甚至整个细胞。在这一章中，我们将在神经发育的离散窗口期间免疫激活会对大脑功能产生深远影响，从而增加神经发育和神经精神疾病风险的框架内讨论这一文献。在这一章中，我们回顾了三个敏感的发育时期——胚胎布线、早期产后突触修剪和青少年回路细化，以突出小胶质细胞在构建大脑过程中所执行的多种功能。在回顾这些文献时，很明显时间因素很重要，也许比免疫激活本身的性质更为重要；小胶质细胞对不同损伤的反应模式很大程度上是保守的，但由于挑战时大脑成熟度的阶段不同，其功能影响也不同。
