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Dysregulation of GABAergic System in the Inferior Colliculi of Rats during the Development of Audiogenic Epilepsy

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Abstract

Epilepsy is tightly associated with dysfunction of inhibitory GABA neurotransmission. In this study, Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures (AGS) were used. KM rats are characterized by the development of audiogenic epilepsy during postnatal ontogenesis, with AGS onset at the age of 1.5–2 months and fully developed AGS expression by 3rd month. We analyzed GABAergic system of the inferior colliculi (IC) of KM rats at different stages of postnatal development. Wistar rats were used as a control. In the IC of young KM rats, Na+/K+/Cl– cotransporter 1 (NKCC1) expression was increased, while K+/Cl– cotransporter 2 (KCC2) was unchanged indicating impairment of postsynaptic GABA action at early stages of postnatal development. Moreover, we revealed also an increase in the expression of vesicular GABA transporter (VGAT) in the IC which additionally pointed on the higher activity of GABA release. In adult rats, in opposite, we revealed a decrease in the expression of KCC2 transporter indicating downregulation of GABA inhibition on the target cells. Thus, GABA dysregulation in the IC can mediate the seizure susceptibility in adult KM rats.

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Fig. 1.
Fig. 2.

Abbreviations

KM:

Krushinsky–Molodkina rats

IC:

inferior colliculi

AGS:

audiogenic seizure

KCC2:

K+/Cl– cotransporter 2

NKCC1:

Na+/K+/Cl– cotransporter

VGAT:

vesicular GABA transporter

GABAAR(α):

GABA-A receptor α1-subunit

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Acknowledgments

Part of the analysis was done at Research Resource Center no. 441590 at Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences.

Funding

This study was supported by the Russian Government Program no. 075-967-23-00.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, the Russian Academy of Sciences, St. Petersburg, Russia

    S. D. Nikolaeva, A. P. Ivlev, A. A. Naumova, A. A. Kulikov, M. V. Glazova & E. V. Chernigovskaya

Authors
  1. S. D. Nikolaeva
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  2. A. P. Ivlev
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  3. A. A. Naumova
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  4. A. A. Kulikov
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  5. M. V. Glazova
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  6. E. V. Chernigovskaya
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Contributions

Conceptualization, S.D.N., E.V.C.; methodology, A.A.N., E.V.C.; formal analysis, A.A.N., A.P.I.,; investigation, A.P.I., S.D.N., A.A.N.; data curation, E.V.C.; writing—original draft preparation, A.P.I., E.V.C.; writing—review and editing, A.A.N., M.V.G.; visualization, A.P.I., S.D.N., A.A.K.; supervision, M.V.G.; funding acquisition, E.V.C. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to M. V. Glazova.

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Ethics Statement

All experiments with rats were conducted in accordance with EC Directive 86/609/EEC for animal experiments and approved by the Institutional Animal Care and Use Committee at the Sechenov Institute of Evolutionary Physiology and Biochemistry (protocol code 6-3/2022, June 23, 2022).

Conflicts of Interest

The authors declare no conflict of interest.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 7, pp. 890–901https://doi.org/10.31857/S0869813923070105.

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Nikolaeva, S.D., Ivlev, A.P., Naumova, A.A. et al. Dysregulation of GABAergic System in the Inferior Colliculi of Rats during the Development of Audiogenic Epilepsy. J Evol Biochem Phys 59, 1252–1261 (2023). https://doi.org/10.1134/S002209302304018X

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