Журнал эволюционной биохимии и физиологии, 2020, T. 56, № 7, стр. 771-771

Structural Reorganization of the Hippocampus of Krushinsky–Molodkina (KM) Rats during Epileptogenesi

A. A. Kulikov 1*, M. V. Glazova 1, E. L. Harbachova 1, E. V. Chernigovskaya 1

1 Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Saint-Petersburg, Russia

* E-mail: alekskulikovaa95@gmail.com

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It is known that seizures provoke neuronal death. The aim of the study was to determine apoptosis and autophagy in the hippocampus of Krushinsky–Molodkina (KM) rats at the different stages of audiogenic kindling.

Methods. Male and female adult KM rats genetically prone to audiogenic seizures (AGS) were used in the experiments. 4, 7 and 25 AGS experienced KM rats were used in the experiments to analyze the seizure-induced alterations in apoptosis and autophagy in the hippocampus. The hippocampi were collected either 24 hours or in a week after the last AGS. Expression of р53, caspase 3, 8 and 9, cytochrome C, Mcl1, Bcl-2, Beclin-1, p62, LC3 was analyzed by Western blot. Histological sections containing the hippocampus were stained for Tunel, LC3B and cathepsin D.

Results. 4 AGS induced neither apoptosis nor autophagy. While 7 AGS led to the activation of p53, decreasing of Bcl-2 expression, and an increase of Tunel positive cell number that accompanied by decreasing of granular cell number. In a week after 7 AGS, we observed the activation of autophagy, which can partly mediate the survival of granular cells. After 25 AGS we did not see any apoptotic cell and autophagy activity, but the cell population in the dentate gyrus was dramatically decreased.

Conclusion. Our data demonstrated the activation of apoptosis and autophagy only in the initial stages of audiogenic kindling. We suggest that these processes actively contribute to epileptogenesis and fast reorganization of the hippocampal network towards epileptic phenotype.

Supported by RFBR 19-015-00070 and state assignment.

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