Jin Dongdong, Zhang Min, Shi Lei, Liu Hengfang
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Int J Neuropsychopharmacol. 2024 Dec 28;28(1). doi: 10.1093/ijnp/pyae038.
Alzheimer disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly, characterized by severe cognitive impairment and memory loss. Emerging evidence suggests that neuroinflammation plays a significant role in AD pathogenesis, with cytokines like interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) contributing to the disease progression.
We utilized Gene Expression Omnibus datasets to identify IL-6 and CXCL8 as pivotal inflammatory markers in AD. In vitro experiments were conducted using SK-N-BE(2)-M17 and THP-1 cell lines treated with IL-6 and CXCL8 to model AD. Additionally, in vivo tests on Amyloid Precursor Protein/Presenilin 1 (APP/PS1) AD mouse models were performed to assess the impact of these cytokines on cognitive functions and brain pathology.
The results indicated a significant decrease in cell viability, increased apoptosis, and elevated inflammatory factor secretion following IL-6 and CXCL8 treatment in vitro. In vivo, AD mouse models treated with these cytokines exhibited exacerbated emotional distress, decreased social interaction, impaired cognitive functions, and increased amyloid protein deposition in neural tissues.
The study highlights the detrimental effects of IL-6 and CXCL8 on neuronal health and cognitive functions in AD. These findings suggest that targeting these cytokines could offer potential therapeutic interventions for improving patient outcomes in Alzheimer disease.
阿尔茨海默病(AD)是一种主要影响老年人的进行性神经退行性疾病,其特征为严重的认知障碍和记忆丧失。新出现的证据表明,神经炎症在AD发病机制中起重要作用,白细胞介素-6(IL-6)和C-X-C基序趋化因子配体8(CXCL8)等细胞因子促进疾病进展。
我们利用基因表达综合数据库将IL-6和CXCL8鉴定为AD中的关键炎症标志物。使用经IL-6和CXCL8处理的SK-N-BE(2)-M17和THP-1细胞系进行体外实验以模拟AD。此外,对淀粉样前体蛋白/早老素1(APP/PS1)AD小鼠模型进行体内试验,以评估这些细胞因子对认知功能和脑病理学的影响。
结果表明,体外经IL-6和CXCL8处理后,细胞活力显著降低,凋亡增加,炎症因子分泌升高。在体内,用这些细胞因子处理的AD小鼠模型表现出更严重的情绪困扰、社交互动减少、认知功能受损以及神经组织中淀粉样蛋白沉积增加。
该研究突出了IL-6和CXCL8对AD中神经元健康和认知功能的有害影响。这些发现表明,针对这些细胞因子可能为改善阿尔茨海默病患者的预后提供潜在的治疗干预措施。