Influence of the epileptiform discharge microenvironment on the differentiation of oligodendrocyte precursor cells

Brain Res. 2018 Jan 15:1679:53-63. doi: 10.1016/j.brainres.2017.11.021. Epub 2017 Nov 23.

Abstract

The use of related cell cultured models to investigate the genesis and development of epilepsy is beneficial for exploring the mechanism of epileptogenesis. Recent reports have described the myelination damage caused by epilepsy in animal models; however, limited reports have focused on the influence of epilepsy on remyelination in vitro. The current study was designed to investigate the effect of the epileptiform discharge microenvironment on the differentiation of oligodendrocyte precursor cells (OPCs). Neurons with epileptiform discharge released more glutamic acid than normal neurons, which was detected by HPLC. The RT-qPCR, immunofluorescence and Western Blot results showed myelin basic protein (MBP) loss in the epileptiform discharge neuron microenvironment, with increased GluR2 subunit expression. In addition, an α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor antagonist altered the influence of epilepsy on OPC differentiation. This study confirmed the positive effect of epilepsy on the differentiation of OPCs and verified the critical role of glutamic acid and the AMPA receptor in this process, which provides a potential treatment strategy for epilepsy.

Keywords: AMPA receptor; Differentiation; Epilepsy; GluR2 subunit; Microenvironment; Oligodendrocyte precursor cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Brain / cytology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agents / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Glutamic Acid / metabolism
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Microscopy, Confocal
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism
  • Neurons / chemistry
  • Neurons / drug effects
  • Neurons / physiology
  • Oligodendrocyte Precursor Cells / drug effects
  • Oligodendrocyte Precursor Cells / physiology*
  • Patch-Clamp Techniques
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism

Substances

  • Culture Media, Conditioned
  • Excitatory Amino Acid Agents
  • Mbp protein, rat
  • Myelin Basic Protein
  • RNA, Messenger
  • Receptors, AMPA
  • Glutamic Acid
  • glutamate receptor ionotropic, AMPA 2