Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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外文摘要：Postoperative cognitive dysfunction is a severe complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus 3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chil1 was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fracture surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 1 24 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1β and inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleu kin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein 1 may have therapeutic potential for postoperative cognitive dysfunction.

外文关键词：

Chil1hippocampuslearning and memoryM2 microglianeuroinflammationpostoperative cognitive dysfunction(POCD)recombinant CHI3L1

作者：

Yujia Liu、Xue Han、Yan Su、Yiming Zhou、Minhui Xu、Jiyan Xu、Zhengliang Ma、Xiaoping Gu、Tianjiao Xia

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作者单位：

Department of Anesthesiology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu Province,China

Medical School,Nanjing University,Nanjing,Jiangsu Province,China

Jiangsu Key Laboratory of Molecular Medicine,Nanjing University,Nanjing,Jiangsu Province,China

State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing,Jiangsu Province,China

Department of Anesthesiology,Zhongshan Hospital,Fudan University,Shanghai,China

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01233

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(9)