Long-term consumption of alcohol exacerbates neural lesions by destroying the functional integrity of the blood–brain barrier

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.

Keywords:

• Alcohol consumption
• blood–brain barrier
• functional integrity
• structural integrity
• Alzheimer’s disease
• β-amyloid

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Key Program; No. 81430100].