{"title":"NLRP3抑制剂可缓解血糖变化诱发的2型糖尿病老年大鼠认知功能障碍","authors":"Wei Yang, Si-Cong Si, Jing Li, Yi-Xin Ma, Huan Zhao, Jia Liu","doi":"10.1016/j.mce.2024.112406","DOIUrl":null,"url":null,"abstract":"<p><p>Glycemic variability (GV) markedly exacerbates cognitive impairment in elderly patients with type 2 diabetes mellitus (T2DM), in part through chronic inflammation. This study investigated the therapeutic efficacy of the NLRP3 inflammasome inhibitor MCC950 in mitigating GV-induced cognitive impairment in an aged rat model of T2DM. Aged Sprague-Dawley rats with induced T2DM were subjected to GV conditions, and the effects of MCC950 were evaluated through measurement of body weight, blood glucose, lipid profiles, insulin level, inflammatory markers, and cognitive function. Transcriptomic analysis was performed on the hippocampus and prefrontal cortex. Treatment with MCC950 significantly alleviated weight loss and hyperglycemia in the GV group compared with the control group. MCC950 also reduced the levels of cholesterol, triglycerides, and pro-inflammatory markers (interleukin-1β (IL-1β) and interleukin-18 (IL-18)). Most notably, MCC950 improved spatial learning and memory retention in the GV group. Immunohistochemical analysis indicated a reduction in inflammasome activation and an increase in the expression level of the neuronal marker NeuN in the hippocampus. Transcriptomic analysis revealed that MCC950 altered neuroactive ligand-receptor interaction pathways in the hippocampus and influenced receptor binding and cell adhesion processes in the prefrontal cortex. These findings validated the efficacy of NLRP3 inhibitor in mitigating GV-induced cognitive impairment in elderly rats with T2DM and provided the basis for subsequent clinical studies exploring the broader potential of NLRP3-targeted interventions in addressing diabetes-associated cognitive impairment.</p>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NLRP3 inhibitor alleviates glycemic variability-induced cognitive impairment in aged rats with type 2 diabetes mellitus.\",\"authors\":\"Wei Yang, Si-Cong Si, Jing Li, Yi-Xin Ma, Huan Zhao, Jia Liu\",\"doi\":\"10.1016/j.mce.2024.112406\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Glycemic variability (GV) markedly exacerbates cognitive impairment in elderly patients with type 2 diabetes mellitus (T2DM), in part through chronic inflammation. This study investigated the therapeutic efficacy of the NLRP3 inflammasome inhibitor MCC950 in mitigating GV-induced cognitive impairment in an aged rat model of T2DM. Aged Sprague-Dawley rats with induced T2DM were subjected to GV conditions, and the effects of MCC950 were evaluated through measurement of body weight, blood glucose, lipid profiles, insulin level, inflammatory markers, and cognitive function. Transcriptomic analysis was performed on the hippocampus and prefrontal cortex. Treatment with MCC950 significantly alleviated weight loss and hyperglycemia in the GV group compared with the control group. MCC950 also reduced the levels of cholesterol, triglycerides, and pro-inflammatory markers (interleukin-1β (IL-1β) and interleukin-18 (IL-18)). Most notably, MCC950 improved spatial learning and memory retention in the GV group. Immunohistochemical analysis indicated a reduction in inflammasome activation and an increase in the expression level of the neuronal marker NeuN in the hippocampus. Transcriptomic analysis revealed that MCC950 altered neuroactive ligand-receptor interaction pathways in the hippocampus and influenced receptor binding and cell adhesion processes in the prefrontal cortex. These findings validated the efficacy of NLRP3 inhibitor in mitigating GV-induced cognitive impairment in elderly rats with T2DM and provided the basis for subsequent clinical studies exploring the broader potential of NLRP3-targeted interventions in addressing diabetes-associated cognitive impairment.</p>\",\"PeriodicalId\":18707,\"journal\":{\"name\":\"Molecular and Cellular Endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.mce.2024.112406\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.mce.2024.112406","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
NLRP3 inhibitor alleviates glycemic variability-induced cognitive impairment in aged rats with type 2 diabetes mellitus.
Glycemic variability (GV) markedly exacerbates cognitive impairment in elderly patients with type 2 diabetes mellitus (T2DM), in part through chronic inflammation. This study investigated the therapeutic efficacy of the NLRP3 inflammasome inhibitor MCC950 in mitigating GV-induced cognitive impairment in an aged rat model of T2DM. Aged Sprague-Dawley rats with induced T2DM were subjected to GV conditions, and the effects of MCC950 were evaluated through measurement of body weight, blood glucose, lipid profiles, insulin level, inflammatory markers, and cognitive function. Transcriptomic analysis was performed on the hippocampus and prefrontal cortex. Treatment with MCC950 significantly alleviated weight loss and hyperglycemia in the GV group compared with the control group. MCC950 also reduced the levels of cholesterol, triglycerides, and pro-inflammatory markers (interleukin-1β (IL-1β) and interleukin-18 (IL-18)). Most notably, MCC950 improved spatial learning and memory retention in the GV group. Immunohistochemical analysis indicated a reduction in inflammasome activation and an increase in the expression level of the neuronal marker NeuN in the hippocampus. Transcriptomic analysis revealed that MCC950 altered neuroactive ligand-receptor interaction pathways in the hippocampus and influenced receptor binding and cell adhesion processes in the prefrontal cortex. These findings validated the efficacy of NLRP3 inhibitor in mitigating GV-induced cognitive impairment in elderly rats with T2DM and provided the basis for subsequent clinical studies exploring the broader potential of NLRP3-targeted interventions in addressing diabetes-associated cognitive impairment.
期刊介绍:
Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.