Aim: We investigated the mechanism, whereby tumor necrosis factor‐like ligand 1A (TL1A) mediates the A1 differentiation of astrocytes in postoperative cognitive dysfunction (POCD).Methods: The cognitive and behavioral abilities of mice were assessed by Morris water maze and open field tests, while the levels of key A1 and A2 astrocyte factors were detected by RT‐qPCR. Immunohistochemical (IHC) staining was used to examine the expression of GFAP, western blot was used to assay the levels of related proteins, and enzyme‐linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines.Results: The results showed that TL1A could promote the progression of cognitive dysfunction in mice. Astrocytes differentiated into A1 phenotype, while unobvious changes were noted in astrocyte A2 biomarkers. Knockout of NLRP3 or intervention with NLRP3 inhibitor could inhibit the effect of TL1A, improving the cognitive dysfunction and suppressing the A1 differentiation.Conclusion: Our results demonstrate that TL1A plays an important role in POCD in mice, which promotes the A1 differentiation of astrocytes through NLRP3, thereby exacerbating the progression of cognitive dysfunction.

AimThis study was aimed at exploring the mechanism by which aurantiamide (Aur) targeted NLRP3 to suppress microglial cell polarization. MethodsThe 7-month-old APP/PS1 mice and C57BL/6 mice were applied to be the study objects, and Aur was administered intragastrically to APP/PS1 mice at 10 mg/kg and 20 mg/kg. The changes in the neurocognitive function of mice were measured by Morris Water Maze (MWM) test. In the in vitro experiments, the mouse BV2 cells were employed as the study objects, which were subject to treatment with 10 mu M and 20 mu M Aur and induced with LPS and IFN-gamma in order to activate BV2 cells and induce their M1 polarization. ResultsAur was found to suppress the M1 polarization of mouse microglia, reduce central neuroinflammation, and improve the cognitive function in mice. Meanwhile, Aur suppressed the activation and the expression of NLRP3 inflammasome. The results of experiments in vitro demonstrated that Aur inhibited the activation and M1 polarization of BV2 cells. ConclusionAur targets NLRP3 and suppresses the activation of NLRP3 inflammasome.

The present work explored the mechanism of dimethyl phthalate (DMP, the environmental contaminant) exposure in inducing cognitive impairment. Targets and regulatory networks related to DMP-brain injury-cognitive impairment were analyzed through network pharmacology. DMP exposure was carried out to simulate DMP environmental uptake, whereas Morris water maze was performed for examining cognitive impairment. Additionally, inflammatory cytokine levels within tissues were measured. hematoxylin-eosin staining(H&E) and Nissl staining was conducted to examine brain tissue injury, while Western blot was carried out for identifying protein levels. After applying.Small interfering RNA(siRNA-COX2) and celecoxib-COX2 inhibitors separately, we analyzed impacts of DMP. Besides, in vitro experiments were performed to analyze impacts of DMP on microglial activation. As suggested by network pharmacology,Cyclooxygenase-2-PTGS2 (COX2) showed significant relation to DMP, and it exerted its effect via COX2. Following DMP exposure, mice experienced obvious cognitive impairment and brain damage, besides, microglial cells were activated, and inflammatory cytokines were up-regulated. Applying siRNA-COX2 and celecoxib-COX2 suppressed DMP's impact and mitigated mouse cognitive impairment. Based on in vitro analysis, DMP led to microglial activation and neuroinflammation. DMP exposure causes neuroinflammation via the COX2-regulated microglial activation, thus leading to cognitive impairment. COX2 may serve as the key action target of DMP.