Shen Lin, Wang Zhengxin, Wang Rudan, Chen Xiaoyan, Cheng Saiyu
Department of Neurology, The Second Affiliated Hospital of Army Medical University Chongqing 400037, China.
Department of Neurology and Neurosurgery, The Third Affiliated Hospital of Chongqing Medical University Chongqing 401120, China.
Am J Transl Res. 2021 Sep 15;13(9):10276-10287. eCollection 2021.
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 Ca. We evaluated the role of P2X7R in the initiation of neuroinflammation induced by PSD by focusing on its interaction with Ca 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 Ca 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, Ca accumulation in rat brain tissues, and proinflammatory markers. Moreover, the inhibition of P2X7R activity inhibited Ca accumulation and suppressed proinflammatory markers, whereas the upregulation of P2X7R activity had the opposite effect. Inhibition of the Ca channel further strengthened the effect of P2X7R inhibition on Ca accumulation and proinflammatory markers. The upregulation of P2X7R would initiate Ca accumulation and inflammatory response in brain tissues, which suggests a new therapeutic method for neuroinflammation related with PSD.
神经炎症是中风后抑郁症（PSD）的关键过程。离子型P2X7受体（P2X7R）作为一种对Ca通透的ATP门控非选择性离子通道发挥作用。我们通过关注P2X7R与Ca通道的相互作用，评估了P2X7R在PSD诱导的神经炎症起始中的作用。使用大脑中动脉闭塞（MCAO）模型和慢性轻度应激（CMS）诱导PSD症状。我们使用蔗糖偏好试验和莫里斯水迷宫作为抑郁症筛查试验。通过相关生物学实验检测P2X7R的表达水平、脑组织中Ca的积累以及促炎标志物的水平。MCAO+CMS给药诱导模型大鼠出现快感缺失和记忆缺陷，这表明PSD的发展。PSD症状的进展与P2X7R水平升高、大鼠脑组织中Ca积累以及促炎标志物有关。此外，抑制P2X7R活性可抑制Ca积累并抑制促炎标志物，而P2X7R活性上调则产生相反的效果。抑制Ca通道进一步增强了P2X7R抑制对Ca积累和促炎标志物的作用。P2X7R的上调会引发脑组织中的Ca积累和炎症反应，这为与PSD相关的神经炎症提供了一种新的治疗方法。
