PTPN2 通过改变小胶质细胞表型和抑制炎症，使 STAT3 去磷酸化，从而改善麻醉引起的老年大鼠认知能力下降。

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-29 DOI:10.1016/j.bbadis.2024.167545

Xiaochun Zhao , Xueting Wang , Ziyang Xu , Xiaohan Chang , Yue Tian

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引用次数: 0

摘要

围手术期神经认知障碍（PND）是老年人麻醉后常见的神经系统并发症。蛋白酪氨酸磷酸酶非受体2型（PTPN2）可调节信号转导和激活转录蛋白3（STAT3）的信号转导，从而控制某些器官的炎症，但它在PND中的作用尚不清楚。在此，我们用七氟烷处理 18 个月大的大鼠，构建了一个 PND 模型。PND 大鼠出现神经炎症，同时海马中 PTPN2 的表达显著下降，STAT3 磷酸化上升。Ptpn2 的过表达缓解了 PND 大鼠的行为紊乱，改善了神经元损伤，抑制了神经炎症、炎性体激活、小胶质细胞激活和小胶质细胞表型转换。在七氟烷处理的 HMC3 小胶质细胞中，PTPN2 过表达也能观察到类似的结果，而 PTPN2 沉默则显示出相反的结果。此外，PTPN2 似乎是 T-box 转录因子 2 (TBX2) 的靶标。这些结果为支持 PTPN2 是 PND 进展的调控因子这一观点提供了证据。

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PTPN2 dephosphorylates STAT3 to ameliorate anesthesia-induced cognitive decline in aged rats by altering the microglial phenotype and inhibiting inflammation

Perioperative neurocognitive disorders (PNDs) are common neurological complications after anesthesia in the elderly. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates signal transducer and activator of transcription protein 3 (STAT3) signaling to control inflammation in certain organs, but its role in PNDs remains unknown. Herein, we constructed a PND model in 18-month-old rats by treating them with sevoflurane. PND rats developed neuroinflammation, along with a significant decrease in PTPN2 expression and a rise in STAT3 phosphorylation in the hippocampus. Ptpn2 overexpression alleviated the behavioral disorders of PND rats, ameliorated neuronal injury, inhibited neuroinflammation, inflammasome activation, microglial activation, and microglial phenotype switching. Similar results were observed in sevoflurane-treated HMC3 microglia with PTPN2 overexpression, while PTPN2 silencing showed the opposite results. Additionally, PTPN2 seems to be a target of T-box transcription factor 2 (TBX2). These results contribute to the evidence supporting the idea that PTPN2 is a regulatory factor in PND progression.

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.