塞来昔布
缝隙连接
神经炎症
连接蛋白
行为绝望测验
星形胶质细胞
化学
医学
炎症
内科学
药理学
神经科学
生物
海马体
中枢神经系统
生物化学
抗抑郁药
细胞内
作者
X. Long Zheng,Chengfeng Zhang,Liqing Li,Junrui Ye,Siyu Ren,Zhao Zhang,Xiaoyun He,Shifeng Chu,Nai‐Hong Chen
标识
DOI:10.1016/j.brainresbull.2024.110871
摘要
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to exhibit anti-depressive effects in clinical trials. However, the direct mechanism underlying its effect on neuroinflammation remains unclear. Neuroinflammatory reaction from astrocytes leads to depression, and our previous study found that gap junction disorder between astrocytes aggravated neuroinflammatory reaction in depressed mice. To investigate the potential mechanism of celecoxib's effects on astrocytic gap junctions during the central nervous inflammation-induced depression. Stereotaxic injection of lipopolysaccharide (LPS) into the prefrontal cortex (PFC) to establish a model of major depressive disorder (MDD). Celecoxib was administrated into PFC 15 min after LPS injection. The depressive performance was tested by tail suspension test and forced swimming test, and the levels of proinflammation cytokines were determined at mRNA and protein levels. Resting-state functional connection (rsFC) was employed to assess changes in the default mode network (DMN). Additionally, astrocytic gap junctions were also determined by lucifer yellow (LY) diffusion and transmission electron microscope (TEM), and the expression of connexin 43 (Cx43) was measured by western blotting, quantitative polymerase chain reaction, and immunofluorescence. LPS injection induced significant depressive performance, which was ameliorated by celecoxib treatment. Celecoxib also improved rsFC in the DMN. Furthermore, celecoxib improved astrocytic gap junctions as evidenced by increased LY diffusion, shortened gap junction width, and normalized levels of phosphorylated Cx43. Celecoxib also blocked the phosphorylation of p65, and inhibition of p65 abolished the improvement of Cx43. Anti-depressive effects of celecoxib are mediated, at least in part, by the inhibition of nuclear factor- kappa B (NF-κB) and the subsequent improvement of astrocytic gap junction function
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