Title:P2X7 Receptor as a Potential Target for Major Depressive Disorder
Volume: 22
Issue: 10
关键词:
重度抑郁症、P2X7 受体、小胶质细胞、血脑屏障、慢性压力和炎症细胞因子。
摘要: 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.
