Fig. 3.
The expression and function of 5-HT2B receptors are selectively decreased by sleep deprivation (SD) through P2X7 receptors in astrocytes. Prolonged SD stimulates P2X7Rs by ATP, activated P2X7Rs suppress the phosphorylation of AKT and forkhead box O3 (FoxO3a) in the cytoplasm, and the dephosphorylated FoxO3a accumulates in the nucleus of astrocytes. The increased FoxO3a down-regulates the expression of 5-HT2BRs, and the phosphorylation of signal transducer and activator of transcription 3 (STAT3) is also decreased, which relieves the inhibition of the phosphorylation of cPLA2. The activated cPLA2 promotes the release of arachidonic acid (AA) and prostaglandin E2 (PGE2), eventually causing depression-like behaviors. Red arrows indicate the increase of function; black arrows show stimulatory pathways, while black lines with the bar denote the inhibitory pathway.
Reproduced from Xia et al. 2020 [148] with permission from Springer-Nature.