Ontogeny of the epileptic system in rats of the Krushinsky– Molodkina line with genetically determined audiogenic epilepsy

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Abstract

The development of convulsive proneness of audiogenic epilepsy (AE) and phenotype manifestations of epileptic activity in rats of the Krushinsky – Molodkina (KM) strain, proceeds in parallel with the appearance of seizure EEG patterns followed in this investigation from the age of 2 months age up to 7 months (both in КМ rats). The latencies of the seizure onset reduced with age while the intensity of convulsive seizures increased. In background EEG (no exposure to sound) of KM rats two types of epileptiform discharges (ED) were identified. The first type had the form of high-amplitude generalized “packs” of waves, with animal shuddering. The second type of ED had the form of a generalized non-seizure absence-like “spike-wave” discharges with animal freezing. The duration of single absence-like discharges increased with age. The parallel age-related changes were found between the increase in severity of AE seizure and the increase of generalized absence-like discharges numbers in the forebrain EEG of KM rats, which evidence the development of epileptic system in this strain.

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About the authors

S. А. Litvinova

Federal State Budgetary Scientific Institution “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Author for correspondence.
Email: litvinova_sa@academpharm.ru
Russian Federation, Moscow

A. A. Yakovleva

Federal State Budgetary Scientific Institution “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: litvinova_sa@academpharm.ru
Russian Federation, Moscow

T. А. Voronina

Federal State Budgetary Scientific Institution “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: litvinova_sa@academpharm.ru
Russian Federation, Moscow

N. S. Gladysheva

Federal State Budgetary Scientific Institution “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: litvinova_sa@academpharm.ru
Russian Federation, Moscow

V. V. Radontseva

Federal State Budgetary Scientific Institution “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: litvinova_sa@academpharm.ru
Russian Federation, Moscow

N. M. Surina

Moscow State University M.V. Lomonosova

Email: litvinova_sa@academpharm.ru

Faculty of Biology

Russian Federation, Moscow

I. I. Poletaeva

Moscow State University M.V. Lomonosova

Email: litvinova_sa@academpharm.ru

Faculty of Biology

Russian Federation, Moscow

I. B. Fedotova

Moscow State University M.V. Lomonosova

Email: litvinova_sa@academpharm.ru

Faculty of Biology

Russian Federation, Moscow

A. D. Durnev

Federal State Budgetary Scientific Institution “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: litvinova_sa@academpharm.ru

Academician of the RAS

Russian Federation, Moscow

References

  1. Hildebrand M.S, Dahl H.H, Damiano J.A., et al. Recent advances in the molecular genetics of epilepsy. // Journal of medical genetics. 2013. V. 50(5). P. 271–279.
  2. Garbuz D.G., Davletshin A.A., Litvinova S.A., et al. Rodent Models of Audiogenic Epilepsy: Genetic Aspects, Advantages, Current Problems and Perspectives. // Biomedicines. 2022. 10(11). P. 2934.
  3. Семиохина А.Ф., Федотова И.Б., Полетаева И.И. Крысы линии Крушинского-Молодкиной: исследования аудиогенной эпилепсии, сосудистой патологии и поведения // Журнал высшей нервной деятельности им. И.П. Павлова. 2006. Т. 56 (3). С. 298–316.
  4. Paxinos G., Watson C. The rat brain in stereotaxic coordinates. San Diego, Academic Press. 1997. P. 286.
  5. Islam M.R, Abdullah J.M. Age-dependent Electroencephalographic Differences in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) Model of Absence Epilepsy. // Malays J Med Sci. 2014. V. 21. P. 34–40.
  6. Sitnikova E., van Luijtelaar G. Electroencephalographic precursors of spike-wave discharges in a genetic rat model of absence epilepsy: Power spectrum and coherence EEG analyses. // Epilepsy Research. 2009. V. 84. P. 159–171.
  7. van Luijtelaar E.L., Coenen A.M. Two types of electrocortical paroxysms in an inbred strain of rats. // Neurosci. 1986. V. 70. P. 393–397.
  8. Serikawa T., Mashimo T., Kuramoro T., et al. Advances on genetic rat models of epilepsy. // Exp Anim. 2015. V. 64(1). P. 1–7.
  9. Chuvakova L.N., Funikov S.Y., Rezvykh A.P., et al. Transcriptome of the Krushinsky-Molodkina Audiogenic Rat Strain and Identification of Possible Audiogenic Epilepsy-Associated Genes. // Front. Mol. Neurosci. 2021. V.14. P. 1–16.
  10. Powell K.L., Cain S.M., Ng C., et al. A Cav3.2 T-type calcium channel point mutation has splice-variant-specific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy. // J Neurosci. 2009. V. 29(2). P. 371–80.
  11. Crunelli V., David F., Morais T.P. et al. HCN channels and absence seizures. // Neurobiology of Disease. 2023. V. 181.
  12. Nava C., Dalle C., Rastetter A. et al. De novo mutations in HCN1 cause early infantile epileptic encephalopathy. // Nat. Genet. 2014. V. 46. P. 640–645.
  13. Gauguier D., Luijtelaar G.V., Bihoreau M.T. et al. Chromosomal Mapping of Genetic Loci Controlling Absence Epilepsy Phenotypes in the WAG // Rij Rat. Epilepsia. 2004. V. 45. P. 908–915.
  14. Kanyshkova T.P., Meuth P., Bista Z., et al. Differential regulation of HCN channel isoform expression in thalamic neurons of epileptic and non-epileptic rat strains. // Neurobiol. Dis. 2012. V. 45. P. 450–461.
  15. Cain S.M., Tyson J.R., Jones K.L., et al. Thalamocortical neurons display suppressed burst-firing due to an enhanced Ih current in a genetic model of absence epilepsy. // Pflugers Arch. 2015. V. 467. P. 1367–1382.
  16. Zhao K., Li Y., Lai H. et al. Alterations in HCN1 expression and distribution during epileptogenesis in rats. // Epilepsy Research. 2024. V. 202. 107355.
  17. Damasceno S., Gómez-Nieto R., Garcia-Cairasco N., et al. Top common differentially expressed genes in the epileptogenic nucleus of two strains of rodents susceptible to Audiogenic Seizures: WAR and GASH. // Sal. Front. Neurol. 2020V11. P. 33. doi: 10.3389/fneur.2020.00033.
  18. Díaz-Casado E., Gómez-Nieto R., de Pereda J.M., et al. Analysis of gene variants in the GASH. // Sal model of epilepsy.2020. PLoS One 15:e0229953.

Supplementary files

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2. Fig. 1. Intensity of AE seizures in different periods of ontogenesis of KM rats. LP – latent period of seizure onset. * – p ≤ 0.05 difference from 2 months of KM rats (Kruskal-Wallis test with transition to multiple comparisons according to Dunn).

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3. Fig. 2. ER of two types in KM rats of different ages during 2 hours of EEG recording. Gray columns – polyspikes, shaded columns – absence-like discharges. #, * – p ≤ 0.1, p ≤ 0.05, respectively, the difference from 2 months of KM rats (Kruskal-Ullis criterion with the transition to multiple comparisons according to Dunn).

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4. Fig. 3. Convulsive discharges of the “polyspike” type in the EEG of KM rats. A – 3 months, B – 4 months and C – 7 months animals. Leads: 1 – sensorimotor cortex, left hemisphere, 2 – sensorimotor cortex, right hemisphere, 3 – hypothalamus, 4 – hippocampus. Amplitude calibration – 40 μV/mm.

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5. Fig. 4. Absence-type convulsive discharges in the background EEG of KM rats. Designations as in Fig. 3.

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6. Fig. 5. EEG power spectrum in the background and during absence-like discharge in 2.5–3-month-old rats (A), 4-month-old (B), and 7-month-old (C). The abscissa axis shows the wave frequency from 0.5 to 30 Hz with a step of 1 Hz. L. cortex – sensorimotor cortex, left hemisphere, R. cortex – sensorimotor cortex, right hemisphere, HPT – hypothalamus, HPC – hippocampus.

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