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Features of Brain Astrocyte Damage under the Influence of L-Aminoadipic Acid In Vitro and In Vivo

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Abstract

L-Aminoadipic acid (L-AA) is known to have toxic effects on astroglia. The purpose of the work is to characterize the morphological changes in astrocytes in vitro and in vivo under the influence of L-AA. The effect of L-AA in the concentration range 0.17–1.4 mM on astrocytes was evaluated in primary dissociated cultures of the rat cerebral cortex and cerebellum, as well as upon stereotaxic injection (20 μg) into the striatum of rats. Concentrations of 0.35–1.4 mM L-AA caused a decrease in the expression of acidic glyofibrillar protein (GFAP), damage and death of astrocytes, pyknosis, and activation of lysosomes (increased LAMP2 expression). On the second day after the injection of L-AA into the striatum of rats, an extensive lesion area devoid of GFAP-positive staining was formed. The data obtained showed that the use of L-aminoadipic acid is promising for modeling damage to astroglia in neurodegenerative diseases.

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Funding

The work was carried out at the expense of budgetary funding of the Federal State Budgetary Scientific Institution Scientific Center of Neurology within the framework of a state assignment.

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Authors and Affiliations

  1. Research Center of Neurology, 125367, Moscow, Russia

    D. N. Voronkov, A. A. Lyzhin, Yu. V. Dikalova, A. V. Stavrovskaya, R. M. Khudoerkov & L. G. Khaspekov

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  1. D. N. Voronkov
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  2. A. A. Lyzhin
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  3. Yu. V. Dikalova
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  4. A. V. Stavrovskaya
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  5. R. M. Khudoerkov
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  6. L. G. Khaspekov
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Contributions

Research concept and design—D.N. Voronkov, Yu.V. Dikalova; analysis and interpretation of data— R.M. Khudoerkov, Voronkov D.N., Dikalova Yu.V.; holding experiment and material processing—A.A. Lyzhin, D.N. Voronkov, Yu.V. Dikalova, A.V. Stavrovskaya; statistical processing—D.N. Voronkov, Yu.V. Dikalova; writing work—D.N. Voronkov, R.M. Khudoerkov, Yu.V. Dikalova, L.G. Khaspekov; final editing of the text—R.M. Khudoerkov, L.G. Khaspekov, Yu.V. Dikalova.

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Correspondence to Yu. V. Dikalova.

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Conflict of interest. The authors declare that they have no conflicts of interest.

Statement on the welfare of animals. Manipulations with animals were carried out in accordance with regulatory documents (Principles Good Laboratory Practice 2009, GOST R 53434-200 and EU recommendations “Euthanasia of experimental animals,” 1997, ISBN 92-827-9694-9). The number of the decision of the local ethics committee no. 2-5/19 from February 20, 2019.

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Abbreviations: GFAP—acidic glyofibrillar protein, L-AA—L‑aminoadipic acid.

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Voronkov, D.N., Lyzhin, A.A., Dikalova, Y.V. et al. Features of Brain Astrocyte Damage under the Influence of L-Aminoadipic Acid In Vitro and In Vivo. Cell Tiss. Biol. 15, 347–355 (2021). https://doi.org/10.1134/S1990519X21040106

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