Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer's Disease.

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY

International Journal of Neuropsychopharmacology Pub Date : 2024-09-03 DOI:10.1093/ijnp/pyae038

Dongdong Jin, Min Zhang, Lei Shi, Hengfang Liu

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引用次数: 0

Abstract

Background: Alzheimer's 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.

Methods: We utilized GEO 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.

Results: 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.

Conclusions: 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's disease.

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研究 IL-6 和 CXCL8 对阿尔茨海默病神经变性和认知能力下降的影响

背景：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，其特征是严重的认知障碍和记忆丧失。新的证据表明，神经炎症在阿尔茨海默病的发病机制中起着重要作用，白细胞介素-6（IL-6）和C-X-C motif趋化因子配体8（CXCL8）等细胞因子有助于疾病的进展：我们利用 GEO 数据集确定了 IL-6 和 CXCL8 作为 AD 的关键炎症标记物。体外实验使用经IL-6和CXCL8处理的SK-N-BE（2）-M17和THP-1细胞系来模拟AD。此外，还对淀粉样前体蛋白/Presenilin 1（APP/PS1）AD小鼠模型进行了体内试验，以评估这些细胞因子对认知功能和大脑病理学的影响：结果表明，体外处理 IL-6 和 CXCL8 后，细胞活力明显降低，凋亡增加，炎症因子分泌增加。在体内，用这些细胞因子处理的AD小鼠模型表现出情绪困扰加剧、社会交往减少、认知功能受损以及神经组织中淀粉样蛋白沉积增加：该研究强调了IL-6和CXCL8对AD患者神经元健康和认知功能的不利影响。这些研究结果表明，针对这些细胞因子可提供潜在的治疗干预，改善阿尔茨海默病患者的预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Neuropsychopharmacology 医学-精神病学

CiteScore

8.40

自引率

2.10%

发文量

230

审稿时长

4-8 weeks

期刊介绍： The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.

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