Alcohol-Induced Alterations in the Vascular Basement Membrane in the Substantia Nigra of the Adult Human Brain

Sandra Skuja (Coresponding Author), Nityanand Jain (Coresponding Author), Marks Smirnovs, Modra Murovska

Research output: Contribution to journalArticlepeer-review

Abstract

The blood–brain barrier (BBB) represents a highly specialized interface that acts as the first line of defense against toxins. Herein, we investigated the structural and ultrastructural changes in the basement membrane (BM), which is responsible for maintaining the integrity of the BBB, in the context of chronic alcoholism. Human post-mortem tissues from the Substantia Nigra (SN) region were obtained from 44 individuals, then grouped into controls, age-matched alcoholics, and non-age-matched alcoholics and assessed using light and electron microscopy. We found significantly less CD31+ vessels in alcoholic groups compared to controls in both gray and white matter samples. Alcoholics showed increased expression levels of collagen-IV, laminin-111, and fibronectin, which were coupled with a loss of BM integrity in comparison with controls. The BM of the gray matter was found to be more disintegrated than the white matter in alcoholics, as demonstrated by the expression of both collagen-IV and laminin-111, thereby indicating a breakdown in the BM’s structural composition. Furthermore, we observed that the expression of fibronectin was upregulated in the BM of the white matter vasculature in both alcoholic groups compared to controls. Taken together, our findings highlight some sort of aggregation or clumping of BM proteins that occurs in response to chronic alcohol consumption.

Original languageEnglish
Article number830
JournalBiomedicines
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 2022

Keywords*

  • alcoholism
  • collagen-IV
  • electron microscopy
  • fibronectin
  • laminin-111
  • light microscopy
  • substantia nigra
  • vascular basement membrane

Field of Science*

  • 3.1 Basic medicine
  • 1.6 Biological sciences

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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