Activation of ERK by spontaneous seizures in neural progenitors of the dentate gyrus in a mouse model of epilepsy

作者：Li, Yi; Peng, Zechun; Xiao, Bo; Houser, Carolyn R.^*

来源：Experimental Neurology, 2010, 224(1): 133-145.

DOI：10.1016/j.expneurol.2010.03.003

• Extracellular signal-regulated kinase (ERK)
• Hippocampus
• Dentate gyrus
• Subgranular zone
• Neurogenesis
• Brain lipid binding protein (BLBP)
• Spontaneous seizure
• Pilocarpine
• 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 (similar to 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.

• 出版日期2010-7
• 单位中南大学