Upregulation of the P2X7 receptor promotes Ca2+ accumulation and inflammatory response in post-stroke depression

Neuroinflammation is a critical process in post-stroke depression (PSD). The ionotropic P2X7 receptor (P2X7R) functions as an ATP-gated nonselective ion channel permeable to Ca2+. We evaluated the role of P2X7R in the initiation of neuroinflammation induced by PSD by focusing on its interaction with Ca2+ channels. PSD symptoms were induced using a middle cerebral artery occlusion (MCAO) model and the administration of chronic mild stress (CMS). We used the sucrose preference and Morris Water Maze as depression screening tests. The expression level of P2X7R, accumulation of Ca2+ in brain tissues, and levels of proinflammatory markers were detected by the relevant biological experiments. The administration of MCAO+CMS induced anhedonia and memory deficit in model rats, which was indicative of the development of PSD. The progression of the PSD symptoms was associated with increased levels of P2X7R, Ca2+ accumulation in rat brain tissues, and proinflammatory markers. Moreover, the inhibition of P2X7R activity inhibited Ca2+ accumulation and suppressed proinflammatory markers, whereas the upregulation of P2X7R activity had the opposite effect. Inhibition of the Ca2+ channel further strengthened the effect of P2X7R inhibition on Ca2+ accumulation and proinflammatory markers. The upregulation of P2X7R would initiate Ca2+ accumulation and inflammatory response in brain tissues, which suggests a new therapeutic method for neuroinflammation related with PSD.