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阿尔茨海默病进展中 5xFAD 小鼠模型星形细胞中整合素β-3的上调。

Upregulation of Integrin beta-3 in astrocytes upon Alzheimer's disease progression in the 5xFAD mouse model.

机构信息

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

出版信息

Neurobiol Dis. 2024 Feb;191:106410. doi: 10.1016/j.nbd.2024.106410. Epub 2024 Jan 12.

Abstract

Integrins are receptors that have been linked to various brain disorders, including Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. While Integrin beta-3 (ITGB3) is known to participate in multiple cellular processes such as adhesion, migration, and signaling, its specific role in AD remains poorly understood, particularly in astrocytes, the main glial cell type in the brain. In this study, we investigated alterations in ITGB3 gene and protein expression during aging in different brain regions of the 5xFAD mouse model of AD and assessed the interplay between ITGB3 and astrocytes. Primary cultures from adult mouse brains were used to gain further insight into the connection between ITGB3 and amyloid beta (Aβ) in astrocytes. In vivo studies showed a correlation between ITGB3 and the astrocytic marker GFAP in the 5xFAD brains, indicating its association with reactive astrocytes. In vitro studies revealed increased gene expression of ITGB3 upon Aβ treatment. Our findings underscore the potential significance of ITGB3 in astrocyte reactivity in the context of Alzheimer's disease.

摘要

整合素是与各种脑部疾病相关的受体,包括阿尔茨海默病(AD),这是最常见的神经退行性疾病。虽然整合素β-3(ITGB3)已知参与多种细胞过程,如黏附、迁移和信号转导,但它在 AD 中的具体作用仍知之甚少,特别是在星形胶质细胞中,星形胶质细胞是大脑中的主要神经胶质细胞类型。在这项研究中,我们研究了 5xFAD AD 小鼠模型不同脑区中 ITGB3 基因和蛋白表达在衰老过程中的变化,并评估了 ITGB3 和星形胶质细胞之间的相互作用。我们使用来自成年小鼠大脑的原代培养物来深入了解星形胶质细胞中 ITGB3 和淀粉样蛋白β(Aβ)之间的联系。体内研究表明,在 5xFAD 大脑中,ITGB3 与星形胶质细胞标志物 GFAP 之间存在相关性,表明其与反应性星形胶质细胞有关。体外研究显示,Aβ 处理后 ITGB3 的基因表达增加。我们的研究结果强调了 ITGB3 在阿尔茨海默病中星形胶质细胞反应中的潜在意义。

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