TL1A promotes the postoperative cognitive dysfunction in mice through NLRP3‐mediated A1 differentiation of astrocytes

Abstract

AimWe investigated the mechanism, whereby tumor necrosis factor‐like ligand 1A (TL1A) mediates the A1 differentiation of astrocytes in postoperative cognitive dysfunction (POCD).MethodsThe 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.ResultsThe 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.ConclusionOur 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.

mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice

“…In addition, it has been reported that neuroin ammatory response mediated by the NLRP3 in ammasome was involved in the pathological process of POCD [52]. Using NLPR3-knockout mice and an NLRP3 inhibitor, tissue in ammatory response was signi cantly inhibited, causing amelioration of murine cognitive dysfunction [53]. Our study also supported NLRP3 in ammasome activation in mouse hippocampal microglia after sevo urane exposure, leading to a deterioration in cognitive function.…”

mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice

“…In addition, it has been reported that neuroinflammatory response mediated by the NLRP3 inflammasome was involved in the pathological process of POCD 54 . Using NLPR3-knockout mice and an NLRP3 inhibitor, tissue inflammatory response was significantly inhibited, causing amelioration of murine cognitive dysfunction 55 . Our study also supported NLRP3 inflammasome activation in mouse hippocampal microglia after sevoflurane exposure, leading to a deterioration in cognitive function.…”

Carnosol ameliorates sevoflurane induced cognitive impairment in aged rats by suppressing NLRP3 inflammasome via activation of autophagy

“…Postoperative cognitive dysfunction (POCD) is a type of complication with long-term consequences, defined as impaired memory, attention and information processing that occurs after anesthesia [1]. Studies show that about 10 % of surgery patients as well as 40 % of older patients over the age of 65 develop POCD [2]. Compared to patients without POCD, patients with POCD have significantly higher mortality rates and higher dependence on social security Trop J Pharm Res, November 2023; 22 (11): 2282 [3].…”