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Methyl-beta-Cyclodextrin Alters the Level of Tight Junction Proteins in the Rat Cerebrovascular Endothelium

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Abstract

The blood–brain barrier (BBB) provides optimal conditions for the functioning of brain neurons. The barrier properties of the cerebrovascular (CV) endothelium are determined by the claudin family of proteins and occludin, which are major molecular determinants of selective intercellular transport. Plasma membrane lipids play an important role in forming the structure of tight junctions, being combined with these proteins into lipid rafts. The development of neurodegenerative diseases and psychiatric disorders correlates with changes in claudin levels in the CV endothelium. We studied the effect of methyl-beta-cyclodextrin (MbCD), which causes destabilization of the plasma membrane lipid phase, on claudin-1, -5 and occludin levels in rat brain tissue. Male rats were injected intravenously with MbCD at a dose of 5 mg/kg of body weight, and 30 min later, brain tissue was prepared for Western blot and immunohistochemistry. MbCD induced a significant decrease in the claudin-5 level in the frontal lobes of the rat brain, while claudin-1 and occludin levels remained unchanged. Immunohistochemistry and confocal laser microscopical image analysis confirmed that changes in claudin-5 localization are confined to the CV endothelium. Since claudin-5 is a major contributor to the impermeability of the CV endothelium, we can assume that a change in the orderliness of the raft lipid phase may lead to an increase in intercellular permeability. The results suggest that the lipid environment is an important molecular component of the tight junction in the rat brain CV endothelium, which may be implicated in the maintenance and regulation of the barrier properties of the BBB.

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Funding

This work was funded by the Russian Science Foundation (RSF), grant no. 18-15-00043. The studies were carried out using the facilities of the “Center for Molecular and Cellular Technologies” Resource Center (project no. 109-14629) and the “Chromas” Center for Collective Use of Equipment (project no. 101-14625) at the St. Petersburg State University.

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Authors and Affiliations

  1. Department of General Physiology, St. Petersburg State University, St. Petersburg, Russia

    A. G. Markov, A. E. Bikmurzina, A. A. Fedorova & I. I. Krivoi

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  1. A. G. Markov
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  2. A. E. Bikmurzina
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  3. A. A. Fedorova
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  4. I. I. Krivoi
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Contributions

Conceptualization and methodology (A.G.M., I.I.K.); data collection and processing (A.E.B., A.A.F.), manuscript writing and editing (A.G.M., A.E.B., A.A.F., I.I.K.).

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Correspondence to A. G. Markov.

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CONFLICT OF INTEREST

The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article. A.G.M. is a member of the editorial board of the Russian Journal of Physiology.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 5, pp. 677–685https://doi.org/10.31857/S0869813922050089.

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Markov, A.G., Bikmurzina, A.E., Fedorova, A.A. et al. Methyl-beta-Cyclodextrin Alters the Level of Tight Junction Proteins in the Rat Cerebrovascular Endothelium. J Evol Biochem Phys 58, 849–855 (2022). https://doi.org/10.1134/S0022093022030188

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