Activation of ERK by Spontaneous Seizures in Neural Progenitors of the Dentate Gyrus in a Mouse Model of Epilepsy

Exp Neurol. 2010 Jul;224(1):133-45. doi: 10.1016/j.expneurol.2010.03.003. Epub 2010 Mar 10.

Abstract

Cellular changes that are associated with spontaneous seizures in temporal lobe epilepsy are not well understood but could influence ongoing epilepsy-related processes. In order to identify cell signaling events that could occur at the time of spontaneous seizures, the localization of phosphorylated extracellular signal-regulated kinase (pERK) was studied in a pilocarpine mouse model of epilepsy at very short intervals (1.5-2.5 min) after detection of a spontaneous seizure. Within the hippocampal formation, immunolabeling of pERK was evident in a subpopulation of cells in the subgranular zone (SGZ) of the dentate gyrus at these short intervals. Many of these cells had a long vertical process and resembled radial glia, while others had short processes and were oriented horizontally. Labeling with a series of developmental markers demonstrated that virtually all pERK-labeled cells were neural progenitor cells (NPCs). A high percentage ( approximately 80%) of the pERK-labeled cells was labeled with either glial fibrillary acidic protein or brain lipid binding protein, indicating that these cells were radial glia-like NPCs. A smaller percentage of labeled cells expressed NeuroD, suggesting that they were later-developing NPCs that were assuming a neuronal identity. Early expression of pERK was not detected in immature neurons. Double labeling with proliferation markers demonstrated that approximately 30% of pERK-labeled NPCs expressed Mcm2, indicating that they were actively proliferating. Furthermore, virtually all radial glia-like NPCs that were in the proliferative cycle expressed pERK. These findings suggest that spontaneous seizures and associated ERK activation could contribute to the proliferation of radial glia-like NPCs in this epilepsy model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Count
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Neurogenesis / physiology*
  • Neuroglia / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Phosphorylation / physiology
  • Pilocarpine
  • Random Allocation
  • Seizures / chemically induced
  • Seizures / metabolism*

Substances

  • Glial Fibrillary Acidic Protein
  • Pilocarpine
  • Extracellular Signal-Regulated MAP Kinases