Emotion, Cognition and Behavior Research Group, Korea Brain Research Institute, Daegu, South Korea; Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, South Korea.
Department of Pharmacology and Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Biol Psychiatry. 2021 Jul 15;90(2):74-84. doi: 10.1016/j.biopsych.2020.11.007. Epub 2020 Nov 17.
Chronic stress causes physiological and hormonal adaptations that lead to neurobiological consequences and behavioral and cognitive impairments. In particular, chronic stress has been shown to drive reduced neurogenesis and altered synaptic plasticity in brain regions that regulate mood and motivation. The neurobiological and behavioral effects of stress resemble the pathophysiology and symptoms observed in psychiatric disorders, suggesting that there are similar underlying mechanisms. Accumulating evidence indicates that neuroimmune systems, particularly microglia, have a critical role in regulating the neurobiology of stress. Preclinical models indicate that chronic stress provokes changes in microglia phenotype and increases inflammatory cytokine signaling, which affects neuronal function and leads to synaptic plasticity deficits and impaired neurogenesis. More recent work has shown that microglia can also phagocytose neuronal elements and contribute to structural remodeling of neurons in response to chronic stress. In this review we highlight work by the Duman research group (as well as others) that has revealed how chronic stress shapes neuroimmune function and, in turn, how inflammatory mediators and microglia contribute to the neurobiological effects of chronic stress. We also provide considerations to engage the therapeutic potential of neuroimmune systems, with the goal of improving treatment for psychiatric disorders.
慢性应激会引起生理和激素适应，导致神经生物学后果以及行为和认知障碍。具体而言，慢性应激已被证明会减少调节情绪和动机的大脑区域的神经发生和改变突触可塑性。应激的神经生物学和行为效应类似于精神疾病中观察到的病理生理学和症状，这表明存在类似的潜在机制。越来越多的证据表明，神经免疫系统，特别是小胶质细胞，在调节应激的神经生物学方面起着关键作用。临床前模型表明，慢性应激会引起小胶质细胞表型的变化，并增加炎症细胞因子信号，从而影响神经元功能，导致突触可塑性缺陷和神经发生受损。最近的研究表明，小胶质细胞还可以吞噬神经元成分，并响应慢性应激导致神经元结构重塑。在这篇综述中，我们强调了 Duman 研究小组（以及其他小组）的工作，这些工作揭示了慢性应激如何塑造神经免疫功能，以及炎症介质和小胶质细胞如何促成慢性应激的神经生物学效应。我们还提供了一些考虑因素，以利用神经免疫系统的治疗潜力，目标是改善精神疾病的治疗效果。
