Skip to main content

Analysis of Neural Stem Cells from Krushinskii–Molodkina Rats, Which Have a Genetic Predisposition to Audiogenic Seizures

Epilepsy is known to be associated with impairment to neurogenesis processes. Studies have identified a number of genes whose mutations are liked with the development of inherited forms of epilepsy, and some of these genes are involved in controlling the proliferation and differentiation of neural stem cells (NSC). These data led us to the hypothesis that the development of aberrant neurogenesis may be genetically determined and is the cause of the development of epilepsy driven by genetic etiology. This study was performed in vitro on NSC isolated from the hippocampus of Krushinskii–Molodkina (KM) rats on days 14–17 of postnatal development. Rats of the inbred strain KM, which were bred from the Wistar strain, are genetically predisposed to audiogenic seizures and provide a model of audiogenic epilepsy. Controls consisted of NSC from the hippocampus of Wistar rats. Cell cultures were incubated for 10 days in medium containing retinoic acid to stimulate differentiation. Levels of NSC proliferation were assessed by supplementing the medium with bromodeoxyuridine (BrdU). These results showed that the level of NSC proliferation in KM rats was significantly lower than that in Wistar rats and that KM NSC differentiated more quickly. Analysis of the directions of differentiation showed that NSC from KM rats differentiated predominantly into glutamatergic and catecholaminergic neurons. These data provide evidence that an increased level of maturation of glutamatergic neurons in the hippocampus of KM rats is genetically determined and may be one of the main factors responsible for the development of epileptiform activity in these rats.

This is a preview of subscription content, access via your institution.


  1. 1.

    R. Bai, G. Gao, Xing Y, and H. Xue, “Two outward potassium current types are expressed during the neural differentiation of neural stem cells,” Neural Regen. Res., 8, No. 28, 2656–2665 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    G. A. Baltus, M. P. Kowalski, H. Zhai, et al., “Acetylation of sox2 induces its nuclear export in embryonic Stem Cells,” Stem Cells, 27, No. 9, 2175–2184 (2009).

    Article  CAS  Google Scholar 

  3. 3.

    D. P. Bonislawski, E. P. Schwarzbach, and A. S. Cohen, “Brain injury impairs dentate gyrus inhibitory efficacy,” Neurobiol. Dis., 25, No. 1, 163–169 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    A. Borgkvist, T. Malmlof, K. Feltmann, et al., “Dopamine in the hippocampus is cleared by the norepinephrine transporter,” Int. J. Neuropsychopharmacol., 15, No. 4, 531–540 (2012).

    CAS  PubMed  Google Scholar 

  5. 5.

    K. Jakubs, A. Nanobashvili, S. Bonde, et al., “Environment matters: synaptic properties of Neurons born in the epileptic adult brain develop to reduce excitability,” Neuron, 52, No. 6, 1047–1059 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    J. Jin, H. Suzuki, S. Hirai, et al., “JNK phosphorylates Ser332 of doublecortin and regulates its function in neurite extension and neuronal migration,” Dev. Neurobiol., 70, No. 14, 929–942 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Z. Jin, L. Liu, W. Bian, et al., “Different transcription factors regulate nestin gene expression during P19 cell neural differentiation and central nervous system development,” J. Biol. Chem., 28, 12, 8160–8173 (2009).

    Article  CAS  Google Scholar 

  8. 8.

    H. T. Kao, P. Li, H. M. Chao, et al., “Early involvement of synapsin III in neural progenitor cell development in the adult hippocampus,” J. Comp. Neurol., 507, No. 6, 1860–1870 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    C. G. McNamara and D. Dupret, “Two sources of dopamine for the hippocampus,” Trends Neurosci., 40, No. 7, 383–384 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    P. J. Morgan, R. Hubner, A. Rolfs, and M. F. Frech, “Spontaneous calcium transients in human neural progenitor cells mediated by transient receptor potential channels,” Stem Cells Dev., 22, No. 18, 2477–2486 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    C. T. Myers and H. C. Mefford, “Advancing epilepsy genetics in the genomic era,” Genome Med., 7, 91 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Z. Nicola, K. Fabel, and G. Kempermann, “Development of the adult neurogenic niche in the hippocampus of mice,” Front. Neuroanat., 9, 53 (2015).

  13. 13.

    M. Pallotto and F. Deprez, “Regulation of adult neurogenesis by GABAergic transmission: signaling beyond GABAA-receptors,” Front. Cell. Neuroscience, 8, 166 (2014).

  14. 14.

    J. M. Parent, R. C. Elliott, S. J. Pleasure, et al., “Aberrant seizure-neurogenesis in experimental temporal lobe epilepsy,” Ann. Neurol., 59, No. 1, 81–91 (2006).

    Article  PubMed  Google Scholar 

  15. 15.

    J. M. Parent and M. M. Kron, “Neurogenesis and epilepsy,” in: Jasper’s Basic Mechanisms of the Epilepsies, J. L. Noebels (ed.), Bethesda, (2012).

  16. 16.

    L. H. Pevny and S. K. Nicolis, “Sox2 roles in neural stem cells,” Int. J. Biochem. Cell. Biol., 42, No. 3, 421–424 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    A. E. Rosser, P. Tyers, M. ter Borg, et al., “Co-expression of MAP-2 and GFAP in cells developing from rat EGF responsive precursor cells,” Brain Res. Dev. Brain Res., 98, No. 2, 291–295 (1997).

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    H. E. Scharfman, J. H. Goodman, and A. L. Sollas, “Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: functional implications of seizure-induced neurogenesis,” J. Neurosci., 20, No. 16, 6144–6158 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    S. Tanaka, Y. Kamachi, A. Tanouch, et al., “Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells,” Mol. Cell. Biol., 24, No. 20, 8834–8846 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    F. M. Werner and R. Covenas, “Review: classical neurotransmitters and neuropeptides involved in generalized epilepsy in a multi-neurotransmitter system: How to improve the antiepileptic effect?” Epilepsy Behav., 71, Pt. B, 124–129 (2017).

  21. 21.

    T. Yasuda and D. J. Adams, “Physiological roles of ion channels in adult neural stem cells and their progeny,” J. Neurochem., 114, No. 4, 946–959 (2010).

    CAS  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to M. V. Glazova.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 104, No. 2, pp. 226–237, February, 2018.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Saparova, V.B., Zosen, D.V., Nasluzova, E.V. et al. Analysis of Neural Stem Cells from Krushinskii–Molodkina Rats, Which Have a Genetic Predisposition to Audiogenic Seizures. Neurosci Behav Physi 49, 765–772 (2019).

Download citation


  • epilepsy
  • Krushinskii–Molodkina rats
  • hippocampus neural stem cells
  • neuronal differentiation