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Age-Dependent Generation of Epileptiform Activity in the 4-Aminopyridine Model with Slices of the Rat Entorhinal Cortex

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Abstract

Children are more likely to develop epileptic seizures (ictal discharges lasting tens of seconds) than adults. A higher predisposition of the juvenile brain to the generation of epileptiform activity is thought to be due to a prevalence of inhibition over excitation at the early stage of brain development. However, the molecular and physiological mechanisms underlying these age-related differences are yet to be clarified. We compared the ictal activity induced by a convulsant 4-aminopyridine (4-AP) in the horizontal slices of the entorhinal cortex and hippocampus of 3- and 8-week-old Wistar rats. In 3-week-old rats, the ictal discharge was always preceded by a detectable preictal activity, as manifested in one or several 3–4-s GABA-glutamate events, whereas in 8-week-old rats, such events were typically absent or very rare (no more than one occasional short event). The ictal activity resistance to external exposures was also age-dependent. In 8-week-old rats, by contrast to 3-week-old animals, ictal discharge generation in the entorhinal cortex was blocked completely and replaced by 0.2–0.3 Hz interictal activity (simultaneous 1–3-s burst discharges) by a partial blockade of KCC2 cotransporter or Na+–K+-pump, as well as by low-frequency electric stimulation. Thus, our data indicate that ictal discharges in the immature (3-week-old) brain are more resistant to external exposures than in the brain of adult rats. Interictal and ictal epileptiform activities are antagonistic in 8-week-old animals. In contrast, the appearance of interictal activity interrupts the generation of ictal discharges completely. It can therefore be considered as one of the putative antiepileptic mechanisms in the mature rat brain.

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Funding

The reported study was funded by the Russian Foundation for Basic Research, project number 19-315-60016.

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Authors and Affiliations

  1. Almazov National Medical Research Centre, Russian Academy of Sciences, St. Petersburg, Russia

    E. Yu. Smirnova

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

    E. Yu. Smirnova, D. S. Sinyak, A. V. Chizhov & A. V. Zaitsev

  3. Ioffe Institute, Russian Academy of Sciences, St. Petersburg, Russia

    E. Yu. Smirnova & A. V. Chizhov

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  1. E. Yu. Smirnova
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Contributions

E.Yu. Smirnova: experimental design, data collection and processing, writing and editing the manuscript. D.S. Sinyak: data collection on the blockade of the Na+–K+-pump and KCC2 cotransporter in brain slices of 3-week-old rats. A.V. Chizhov and A.V. Zaitsev: data discussion, editing the manuscript.

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Correspondence to E. Yu. Smirnova.

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COMPLIANCE WITH ETHICAL STANDARDS

The experimental protocol met the requirements of the Ethics Committee at the Sechenov Institute of Evolutionary Physiology and Biochemistry (Russian Academy of Sciences) based on international recommendations of the European Communities Council Directive of 1986 (86/609/EEC).

This study did not involve human subjects as research objects.

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The authors have no conflict of interest to declare.

Additional information

Russian Text © The Author(s), 2021, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2021, Vol. 57, No. 2, pp. 144–153https://doi.org/10.31857/S0044452921020078.

Translated by A. Polyanovsky

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Smirnova, E.Y., Sinyak, D.S., Chizhov, A.V. et al. Age-Dependent Generation of Epileptiform Activity in the 4-Aminopyridine Model with Slices of the Rat Entorhinal Cortex. J Evol Biochem Phys 57, 230–240 (2021). https://doi.org/10.1134/S0022093021020058

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