Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Kyungpook National University, Daegu 41940, Republic of Korea.
Cells. 2023 May 31;12(11):1521. doi: 10.3390/cells12111521.
Chronic stress is a major risk factor for various psychiatric diseases, including depression; it triggers various cellular and structural changes, resulting in the alteration of neurocircuitry and subsequent development of depression. Accumulating evidence suggests that microglial cells orchestrate stress-induced depression. Preclinical studies of stress-induced depression revealed microglial inflammatory activation in regions of the brain that regulate mood. Although studies have identified several molecules that trigger inflammatory responses in microglia, the pathways that regulate stress-induced microglial activation remain unclear. Understanding the exact triggers that induce microglial inflammatory activation can help find therapeutic targets in order to treat depression. In the current review, we summarize the recent literature on possible sources of microglial inflammatory activation in animal models of chronic stress-induced depression. In addition, we describe how microglial inflammatory signaling affects neuronal health and causes depressive-like behavior in animal models. Finally, we propose ways to target the microglial inflammatory cascade to treat depressive disorders.
慢性应激是各种精神疾病的一个主要风险因素，包括抑郁症；它会引发各种细胞和结构变化，导致神经回路的改变，随后发展为抑郁症。越来越多的证据表明，小胶质细胞在应激引起的抑郁症中起着协调作用。应激诱导抑郁症的临床前研究显示，小胶质细胞在调节情绪的大脑区域发生炎症激活。尽管研究已经确定了几种触发小胶质细胞炎症反应的分子，但调节应激诱导的小胶质细胞激活的途径仍不清楚。了解诱导小胶质细胞炎症激活的确切触发因素有助于找到治疗靶点，从而治疗抑郁症。在目前的综述中，我们总结了最近关于慢性应激诱导抑郁症动物模型中小胶质细胞炎症激活的可能来源的文献。此外，我们还描述了小胶质细胞炎症信号如何影响神经元健康并在动物模型中引起类似抑郁的行为。最后，我们提出了针对小胶质细胞炎症级联反应的治疗方法来治疗抑郁障碍。
