Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University, Zhejiang, China.
Zhejiang Chinese Medical University, Zhejiang, China.
CNS Neurosci Ther. 2023 Nov;29(11):3588-3597. doi: 10.1111/cns.14290. Epub 2023 Jun 2.
We investigated the mechanism, whereby tumor necrosis factor-like ligand 1A (TL1A) mediates the A1 differentiation of astrocytes in postoperative cognitive dysfunction (POCD).
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.
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.
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.
研究肿瘤坏死因子样配体 1A（TL1A）介导术后认知功能障碍（POCD）中天麻素星形胶质细胞 A1 分化的机制。
通过 Morris 水迷宫和旷场试验评估小鼠的认知和行为能力，通过 RT-qPCR 检测关键 A1 和 A2 星形胶质细胞因子的水平。免疫组织化学（IHC）染色检测 GFAP 的表达，Western blot 检测相关蛋白水平，酶联免疫吸附试验（ELISA）检测炎症细胞因子水平。
结果表明，TL1A 可促进小鼠认知功能障碍的进展。星形胶质细胞分化为 A1 表型，而星形胶质细胞 A2 标志物无明显变化。NLRP3 敲除或 NLRP3 抑制剂干预可抑制 TL1A 的作用，改善认知功能障碍并抑制 A1 分化。
本研究结果表明，TL1A 在小鼠 POCD 中发挥重要作用，通过 NLRP3 促进星形胶质细胞的 A1 分化，从而加重认知功能障碍的进展。
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