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Assessment of the Level of Rage in Cells Blood-Brain Barrier in Experimental Alzheimer’s Disease

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Abstract

Alzheimer’s – disease is a progressive neurodegenerative disorder in which the accumulation of β‑amyloid and neurofibrillary tangles is a determining pathological sign. Activation of RAGE plays a decisive role in the production and aggregation of β-amyloid, formation of neurofibrillary tangles and degeneration of neurons. The aim of this work is to assess the influence of RAGE and its ligands—β-amyloid (Aβ1-42) on endothelial cells of cerebral microvascular in model blood-brain barrier (BBB) in vitro with experimental Alzheimer’s disease. Modeling of experimental Alzheimer’s disease in vitro caused a significant (P ≤ 0.05) increase expression of RAGE on endothelial cells and decrease in the transendothelial electric resistance (TEER) in both the static and dynamic models BBB. However, suppressed expression of RAGE led to a persistent and long-term increase value of TEER. In this case, the ligand RAGE-Ab1-42 caused reduced parameters of TEER. Alzheimer’s disease is accompanied by pathological changes in the expression of RAGE on endothelial cells, thereby leading to altered structural and functional integrity of the BBB. Blocking the RAGE expression in cerebral endothelial cells inhibits development of endothelial dysfunction and restores integrity of BBB impaired by the action of β-amyloid.

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Funding

This work was financially supported by the Program of the President of the Russian Federation for State Support of Leading Scientific Schools of the Russian Federation (S-S-2547.2020.7).

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Authors and Affiliations

  1. Research Institute of Molecular Medicine and Pathobiochemistry, Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of the Russian Federation, 660022, Krasnoyarsk, Russia

    Ya. V. Gorina, E. D. Osipova, A. V. Morgun, E. B. Boytsova, O. L. Lopatina & A. B. Salmina

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  1. Ya. V. Gorina
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  2. E. D. Osipova
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  3. A. V. Morgun
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  4. E. B. Boytsova
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  5. O. L. Lopatina
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  6. A. B. Salmina
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Correspondence to Ya. V. Gorina.

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Conflict of interest. The authors declare no obvious and potential conflicts of interest related to the publication of this article.

Statement on the welfare of animals. The work with animals was carried out in compliance with the principles of humanity, which are set out in the European Community Directive (2010/63/EC). The experiments were carried out with the permission of the Bioethical Commission for Working with Animals at the Local Ethics Committee of the Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenetsky (Excerpt from the protocol no. 7 dated February 11, 2019).

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Abbreviations: AD—Alzheimer’s disease; BBB—blood-brain barrier; TEER—trans endothelial electrical resistance; LRP1— low density lipoprotein receptor-related protein 1 (protein 1, similar to the low density lipoprotein receptor); Aβ1-42—β-amyloid.

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Gorina, Y.V., Osipova, E.D., Morgun, A.V. et al. Assessment of the Level of Rage in Cells Blood-Brain Barrier in Experimental Alzheimer’s Disease. Cell Tiss. Biol. 15, 280–286 (2021). https://doi.org/10.1134/S1990519X21030032

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