Abstract

Recently, increasing numbers of studies have shown that the consumption of large amounts of alcohol is a major risk factor for dementias, which has led to widespread concern about the harmful effects of alcohol consumption on health. However, the pathological changes in the brain caused by this habit are not clear. This study aimed to investigate the possible causes by determining the permeability of the blood–brain barrier (BBB), pathomorphological changes, the mRNA, and protein expressions of adhesion proteins and the concentrations of β-amyloid (Aβ) and some related functional proteins in the brains of C57BL/6 and APPswe/PS1dE9 mice before and after intragastric administration of alcohol for 2 months. The results showed that long-term consumption of alcohol aggravated cognitive decline, increased the permeability of the BBB, led to pathomorphological changes and downregulated some related structural proteins (zonula occludens-1, VE-cadherin, and occludin) and functional proteins (major facilitator superfamily domain-containing protein-2a (Mfsd2a), low-density lipoprotein receptor-related protein-1 (LRP1), receptor for advanced glycation end products (RAGE), and aquaporin-4 (AQP4)) in the BBB but did not increase the concentration of Aβ_1-42. These novel findings suggested that long-term consumption of alcohol induces neural lesions, which is related to the destruction of the integrity of the BBB.

摘要

最近，越来越多的研究表明，大量饮酒是痴呆症的主要危险因素，这引起了人们对饮酒对健康有害影响的广泛关注。然而，这种习惯引起的大脑病理变化尚不清楚。本研究旨在通过测定血脑屏障 (BBB) 的通透性、病理形态学变化、粘附蛋白的 mRNA 和蛋白表达以及 β-淀粉样蛋白 (Aβ) 和一些相关功能蛋白的浓度来探讨可能的原因。 C57BL/6 和 APPswe/PS1dE9 小鼠在灌胃 2 个月前后的大脑。结果表明，长期饮酒会加重认知能力下降，增加血脑屏障的通透性，_1-42。这些新发现表明，长期饮酒会导致神经损伤，这与 BBB 完整性的破坏有关。