Curcumin amends Ca²⁺ dysregulation in microglia by suppressing the activation of P2X7 receptor

Curcumin (Cur) is widely used as an anti-inflammation agent and has anti-depression potential. Neuroinflammation mediated by Ca²⁺ channel activation is closely associated with the progression of post-stroke depression (PSD). In the current study, the role of P2X7 receptor (P2X7R) in the anti-PSD function of Cur was explored. Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and chronic mild stress administration to induce PSD symptoms and then treated with Cur. The behaviors of rats were assessed with sucrose preference and forced swim tests. The accumulation of Ca²⁺ and the systemic inflammatory response in rats were detected. To determine the role of P2X7R in the anti-PSD function of curcumin, the PSD mice were further administrated with P2X7R agonist and antagonist. The administration of Cur attenuated behavior disorders associated with PSD. Moreover, the Ca²⁺ accumulation and the inflammatory response associated with PSD were also blocked by Cur. Cur also inhibited the activation of Ca²⁺ channel. The induced activity of P2X7R blocked the function of Cur by maintaining the symptoms of PSD in Cur-treated rats. Collectively, the anti-PSD function of Cur was dependent on the inhibition of P2X7R, which then deactivated Ca²⁺ channel-mediated inflammatory response associated with PSD progression.