Interleukin-6 induces cognitive impairment via toll-like receptor 4(TLR4)-mediated neuroinflammation and neurodegeneration in mice with chronic kidney disease

作     者：Yangping Shentu Shuqing Ma Simin Ye Yaozhe Ying Luhui Wang Yun Zhu YunTing Wang Nan Jiang Zongyuan Zhao Chenfei Zheng Chaosheng Chen Yongheng Bai Ying Zhou Yangping Shentu;Shuqing Ma;Simin Ye;Yaozhe Ying;Luhui Wang;Yun Zhu;YunTing Wang;Nan Jiang;Zongyuan Zhao;Chenfei Zheng;Chaosheng Chen;Yongheng Bai;Ying Zhou

作者机构：Department of PathologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Wenzhou Medical UniversityWenzhouZhejiangChina Department of NephrologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Pharmacological and Pharmaceutical SciencesCollege of PharmacyUniversity of HoustonHoustonTexasUSA Institute of Chronic NephropathyWenzhou Medical UniversityWenzhouZhejiangChina Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and TranslationThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina 

出 版 物：《Neuroprotection》 (神经保护（英文）)

年 卷 期：2024年第2卷第3期

页      面：203-215页

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：Zhejiang Provincial Outstanding Youth Science Foundation,Grant/Award Numbers:2023C35009,LTGY23H050003,LTGY24H050004 Scienceand Technology Plan Project of Wenzhou Municipality,Grant/Award Numbers:Y2020024,Y20210162,Y2023065 Wenzhou Medical University,Grant/Award Number:XY2022007 

主　　题：5/6 nephrectomy chronic kidney disease cognitive impairment IL-6 TLR4 

摘      要：Backgrounds:Past epidemiological and experimental studies in rodents have demonstrated that chronic kidney disease(CKD)leads to cognitive ***,the underlying mechanism requires further ***,a mouse model of CKD was established using conventional 5/6 *** aimed to examine the relationship between CKD and cognitive impairment and elucidate the underlying ***:Cognitive behavior was assessed using the Morris water maze,novel object recognition test,and fear conditioning *** experiments were also conducted to investigate the underlying molecular ***:Our clinical data revealed a decrease in cognitive function among patients with CKD,accompanied by elevated plasma levels of pro-inflammatory cytokines.A positive correlation between cytokine concentrations and serum creatinine levels,as well as a significant positive correlation with cognitive dysfunction,were *** analyzes demonstrated that hippocampal cytokine levels were positively correlated with serum creatinine levels and cognitive dysfunction in CKD model ***,20 mg/mL interleukin-6(IL-6)significantly decreased HT22 cell activity in ***,HT22 cells treated with IL-6 showed increased expression levels of toll-like receptor 4(TLR4)and myeloid differentiation primary response gene 88(MyD88),thereby inducing the nuclear factor kappa-B p65 inflammatory pathway and mitochondria-dependent *** CKD mouse model showed increased expression of TLR4 and cytokines in the ***4 knockdown antagonized the IL-6-mediated pro-inflammatory and pro-apoptotic effects in HT22 ***4 knockdown in the CKD model mice decreased hippocampal inflammation and increased the number of neuron dendrites,thus ameliorated cognitive ***:These results suggest that IL-6 triggers TLR4 activation to induce neuroinflammation and neurodegeneration in CKD,ultimately culminate in cognitive impairment.