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Dexmedetomidine Alleviates Neuroinflammation-Induced Cognitive Impairment by Modulating the NLRP3 Inflammasome Activation Pathway
Vol 38, Issue 6, 2024
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Abstract
Objective: Neuroinflammation-induced cognitive dysfunction (NICD) relies on symptomatic treatment, with no causative treatment strategies available yet. Therefore, comprehensive investigations on the pathogenesis of NICD are crucial for the development of novel and effective therapeutic drugs. Hence, we aimed to elucidate the impact of Dexmedetomidine (Dex) in modulating nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammatory vesicles for improving cognitive dysfunction. Methods: The study employed both cellular and animal models. The HT22 cells were utilized to assess the impact of Dex on Lipopolysaccharide (LPS)-induced neuroinflammation. Cell viability was examined using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and changes in mitochondrial membrane potential were evaluated using the JC-1 kit. Furthermore, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and NLRP3 were analyzed using Enzyme-Linked Immunosorbnent Assay (ELISA) and qPCR techniques. Additionally, NICD was induced in mice using LPS, and cognitive functions were assessed through the Morris water maze experiment. The expression levels of inflammatory markers in the hippocampal tissues of the mice were evaluated using the qPCR method. Results: The Dex treatment was found to restore the LPS-induced reduction in HT22 cell viability (p < 0.05), as well as significantly reduced the cellular levels of TNF-α, IL-1β, IL-6, and NLRP3 (p < 0.05). Furthermore, Dex treatment restored the mitochondrial membrane potential of HT22 cells (p < 0.05). Additionally, we observed that Dex treatment significantly improved the declining cognitive ability of NICD mice (p < 0.05). Conclusion: Dex can protect the learning and memory capabilities of cognitively impaired mice by inhibiting the expression of NLRP3 inflammatory vesicles as well as inflammatory factors.
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Copyright (c) 2024 Rong Chen, Yang Zhang, Jian Tang, Jingsong Zhu, Xi Li, Linghao Wang, Bin Liu, Taichang Chen, Ying Chen, Shimei Li, Songjiang Tang, Baojun Min
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy