Activation of ERK by spontaneous seizures in neural progenitors of the dentate gyrus in a mouse model of epilepsy.
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.
Department of Neurobiology, CHS 73-235, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095-1763, USA.
Yi
Y
Li
Zechun
Z
Peng
Bo
B
Xiao
Carolyn R
CR
Houser
D000818:Animals; D002452:Cell Count; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D010862:Pilocarpine; D011897:Random Allocation; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D010862:Pilocarpine; D048049:Extracellular Signal-Regulated MAP Kinases