Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

Abstract. Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.

[1]  H. Kretzschmar,et al.  Construction and characterization of murine neuroblastoma cell clones allowing inducible and high expression of the prion protein. , 1999, The Journal of general virology.

[2]  A. Constanti,et al.  Effects of felbamate on muscarinic and metabotropic-glutamate agonist-mediated responses and magnesium-free or 4-aminopyridine-induced epileptiform activity in guinea pig olfactory cortex neurons in vitro. , 1996, The Journal of pharmacology and experimental therapeutics.

[3]  Kamran Khodakhah,et al.  The Therapeutic Mode of Action of 4-Aminopyridine in Cerebellar Ataxia , 2010, The Journal of Neuroscience.

[4]  Maiken Nedergaard,et al.  Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. , 2005, Journal of neurophysiology.

[5]  T. Takano,et al.  An astrocytic basis of epilepsy , 2005, Nature Medicine.

[6]  P. Stanton,et al.  Glutamate-induced Exocytosis of Glutamate from Astrocytes* , 2007, Journal of Biological Chemistry.

[7]  Xi-ru Wu,et al.  Effect of recurrent epileptiform discharges induced by magnesium-free treatment on developing cortical neurons in vitro. , 2003, Brain research. Developmental brain research.

[8]  W. Lytton Computer modelling of epilepsy , 2008, Nature Reviews Neuroscience.

[9]  A. Faden,et al.  Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders , 2011, Neurotherapeutics.

[10]  G. Raposo,et al.  Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles , 2008, Biology of the cell.

[11]  S. Schiff,et al.  Interneuron and pyramidal cell interplay during in vitro seizure-like events. , 2006, Journal of neurophysiology.

[12]  S. Rothman,et al.  Focal cooling rapidly terminates experimental neocortical seizures , 2001, Annals of neurology.

[13]  H. Vijverberg,et al.  Neuroblastoma cells as possible model in the study of glutamate receptors , 1991, Amino Acids.

[14]  I. Osorio,et al.  Stochastic Modeling and Prediction of Experimental Seizures in Sprague‐Dawley Rats , 2001, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[15]  Benjamin J. Whalley,et al.  Investigation of the effects of the novel anticonvulsant compound carisbamate (RWJ‐333369) on rat piriform cortical neurones in vitro , 2009, British journal of pharmacology.

[16]  E. Gruenstein,et al.  Mechanism of synchronized Ca2+ oscillations in cortical neurons , 1997, Brain Research.

[17]  A. Sakamoto,et al.  Cellular Prion Protein: Implications in Seizures and Epilepsy , 2002, Cellular and Molecular Neurobiology.

[18]  P S Albert,et al.  A two-state Markov mixture model for a time series of epileptic seizure counts. , 1991, Biometrics.

[19]  S. Ratté,et al.  The University of Birmingham ( Live System ) Threshold for epileptiform activity is elevated in prion knockout mice , 2016 .