重度抑郁症(MDD)是一种常见的精神障碍。虽然遗传、生化和心理因素都与MDD的发生有关,但普遍认为慢性应激引起的脑部一系列病理变化是MDD的主要原因。然而,慢性压力引起的 MDD 的具体机制在很大程度上被破坏了。最近的研究发现,脑内小胶质细胞促炎细胞因子的增加和炎症通路的变化是 MDD 的潜在病理生理机制。P2X7 受体 (P2X7R) 及其介导的信号通路在小胶质细胞激活中起关键作用。本综述旨在展示和讨论有关 P2X7R 在 MDD 中作用的累积数据。首先,我们总结了 P2X7R 与 MDD 相关性的研究进展。随后,我们介绍了 MDD 中 P2X7R 介导的小胶质细胞激活以及 P2X7R 在由慢性压力引起的血脑屏障 (BBB) 通透性增加中的作用。最后,我们还讨论了慢性压力后 P2X7R 表达变化的潜在机制。总之,P2X7R 是调节小胶质细胞活化的关键分子。慢性应激通过分泌白细胞介素-1β(IL-1β)等炎症细胞因子激活海马小胶质细胞,增加血脑屏障通透性,从而促进MDD的发生和发展,表明P2X7R可能是MDD的一个有前景的治疗靶点。我们展示了 MDD 中 P2X7R 介导的小胶质细胞激活以及 P2X7R 在由慢性压力引起的血脑屏障 (BBB) 通透性增加中的作用。最后,我们还讨论了慢性压力后 P2X7R 表达变化的潜在机制。总之,P2X7R 是调节小胶质细胞活化的关键分子。慢性应激通过分泌白细胞介素-1β(IL-1β)等炎症细胞因子激活海马小胶质细胞,增加血脑屏障通透性,从而促进MDD的发生和发展,表明P2X7R可能是MDD的一个有前景的治疗靶点。我们展示了 MDD 中 P2X7R 介导的小胶质细胞激活以及 P2X7R 在由慢性压力引起的血脑屏障 (BBB) 通透性增加中的作用。最后,我们还讨论了慢性压力后 P2X7R 表达变化的潜在机制。总之,P2X7R 是调节小胶质细胞活化的关键分子。慢性应激通过分泌白细胞介素-1β(IL-1β)等炎症细胞因子激活海马小胶质细胞,增加血脑屏障通透性,从而促进MDD的发生和发展,表明P2X7R可能是MDD的一个有前景的治疗靶点。P2X7R 是调节小胶质细胞活化的关键分子。慢性应激通过分泌白细胞介素-1β(IL-1β)等炎症细胞因子激活海马小胶质细胞,增加血脑屏障通透性,从而促进MDD的发生和发展,表明P2X7R可能是MDD的一个有前景的治疗靶点。P2X7R 是调节小胶质细胞活化的关键分子。慢性应激通过分泌白细胞介素-1β(IL-1β)等炎症细胞因子激活海马小胶质细胞,增加血脑屏障通透性,从而促进MDD的发生和发展,表明P2X7R可能是MDD的一个有前景的治疗靶点。
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P2X7 Receptor as a Potential Target for Major Depressive Disorder
Major depressive disorder (MDD) is a common mental disorder. Although the genetic, biochemical, and psychological factors have been related to the development of MDD, it is generally believed that a series of pathological changes in the brain caused by chronic stress is the main cause of MDD. However, the specific mechanisms underlying chronic stress-induced MDD are largely undermined. Recent investigations have found that increased pro-inflammatory cytokines and changes in the inflammatory pathway in the microglia cells in the brain are the potential pathophysiological mechanism of MDD. P2X7 receptor (P2X7R) and its mediated signaling pathway play a key role in microglia activation. The present review aimed to present and discuss the accumulating data on the role of P2X7R in MDD. Firstly, we summarized the research progress in the correlation between P2X7R and MDD. Subsequently, we presented the P2X7R mediated microglia activation in MDD and the role of P2X7R in increased blood-brain barrier (BBB) permeability caused by chronic stress. Lastly, we also discussed the potential mechanism underlying-P2X7R expression changes after chronic stress. In conclusion, P2X7R is a key molecule regulating the activation of microglia. Chronic stress activates microglia in the hippocampus by secreting interleukin- 1β (IL-1β) and other inflammatory cytokines, and increasing the BBB permeability, thus promoting the occurrence and development of MDD, which indicated that P2X7R might be a promising therapeutic target for MDD.